Changes in the substitutions at C-3 and C-5 positions of 4-(1-methyl-5-nitro-2-imidazolyl) dihydr... more Changes in the substitutions at C-3 and C-5 positions of 4-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine have led to changes in potency of the compounds. The objective of the present study was to examine the hypotensive effects of 5 newly synthesized dihydropyridine derivatives of nifedipine in rats with phenylephrine-raised blood pressure. Anesthetized Sprague-Dawley rats were randomly assigned to 19 groups of 7 animals each. Control group received the vehicle dimethylsulfoxide (0.05 mL), 3 groups were given nifedipine at 100, 300, or 1000 g/kg, and 5 other groups each composed of 3 subgroups administered one of the 5 new dihydropyridine compound at 100, 300, or 1000 g/kg. All animals were initially infused with 20 µg/kg/min phenylephrine for 45 min, and were then given a bolus of either dimethylsulfoxide, nifedipine, or new dihydropyridine compounds 20 min after the commencement of phenylephrine infusion. Blood pressure and heart rate (HR) of the animals were measured before and at the end of phenylephrine infusion, or 25 min after injection of vehicle or compounds. Compared to dimethylsulfoxide, nifedipine, and new 1, 4-dihydropyridine derivatives caused significant reductions in MBP. Moreover, cyclohexyl propyl, phenyl butyl, and cyclohexyl methyl analogs of 1, 4-dihydro-2,6-dimethyl-4-(1-methyl-5-nitro-2-imidazoyl)-3,5-pyridinedicarboxylase at 100 g/kg, phenyl butyl, and cyclohexyl methyl analogs at 300 g/kg, and cyclohexyl methyl analogs at 1000 g/kg reduced MBP similar to nifedipine. There was no significant difference between HR of all groups before and after administration of the compounds. The findings indicated that changes in substitution at C-3 and C-5 positions of 2-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine were associated with changes in hypotensive activity of the compounds.
Background: The role of Renin Angiotensin System (RAS) in ischemic/reperfusion (I/R) injuries is ... more Background: The role of Renin Angiotensin System (RAS) in ischemic/reperfusion (I/R) injuries is not fully elucidated. Furthermore, it is not clear whether inhibition of RAS by Angiotensin-Converting Enzyme (ACE) inhibitors has beneficial effects in terms of protecting the brain from I/R injuries. In this study enalapril is used as an ACE inhibitor to evaluate the role of RAS in I/R injuries in the rat. Methods: ACE inhibition was performed one hour before induction of ischemia using a single IP injection of 0.03 mg/kg or 0.1 mg/kg enalapril in the rats. Transient focal cerebral ischemia was induced by 60 min occlusion of the middle cerebral artery followed by reperfusion. Neurological deficit score (NDS) test was performed 24 hours after the start of reperfusion. Finally the animals were sacrificed under deep anesthesia, the brain removed and prepared for the evaluation of cortical and striatal infarction volumes using Triphenyltetrazolium chloride staining method. Results: Pre-ischemic inhibition of ACE with non-hypotensive dose of enalapril (0.03mg/kg) significantly reduced cortical and striatal infarction volumes of ischemic rats by 41.6% and 52.7% respectively with concomitant improvements in NDS. However, no improvement was observed when ACE inhibition accompanied with arterial hypotension. Conclusion: In the rat model of transient focal cerebral ischemia, ACE inhibition seems to reduce the severity of I/R injuries. Therefore, it is plausible to conclude that renin-angiotensinsystem may participate in ischemic/reperfusion injuries.
The first part of this thesis examined the acute cardiovascular effects of CGS 21680, a selective... more The first part of this thesis examined the acute cardiovascular effects of CGS 21680, a selective adenosine A 2 A receptor agonist, relative to those of sodium nitroprusside (SNP) and vehicle (normal saline) in male Sprague-Dawley rats with or without acute occlusion or chronic ligation of the left main coronary artery. Rats with chronic coronary ligation were studied 8 weeks after the operation. The second part examined the chronic effects of 17(3-estradiol, the most abundant naturally-occurring estrogen, relative to those of vehicle on in vivo cardiovascular function and response to vasoactive drugs in ovariectomised rats at 7 weeks after ligation of the left coronary artery. It also; examined the effects of 17(3-estradiol on ex vivo contractile and relaxant responses of aortic rings, pulmonary artery rings and portal vein strips to vasoactive drugs. The ovariectomised rats were implanted with 60 days sustained-release pellets containing 17(3-estradiol (1.5 mg) or vehicle one week...
Background and Aims: Triazole derivatives are widely used as anticancer, antituberculosis, antifu... more Background and Aims: Triazole derivatives are widely used as anticancer, antituberculosis, antifungal, antibacterial, and anti-HIV. The present study compared the vasorelaxing activities of 12 triazoles, which were synthesized via an expedient method, with that of acetylcholine (Ach) using rat aortic rings. Methods: Synthesis of β-Hydroxy 1,4-Disubstituted-1,2,3-triazole Derivatives. Epoxide/benzyl bromide (1 mmol), alkyne (1 mmol) and sodium azide (1.1 mmol) were mixed and stirred in water in the presence of the naocatalyst (2 mol %) at room temperature. After the completion of the reaction, the mixture was vacuumfiltered and washed with ethyl acetate. The organic layer was dried over anhydrous Na2SO4. Removal of the solvent under vacuum, followed by purification on silica gel column afforded the pure products. Preparation of the rat aorta. Thoracic aortic rings from 6 normal Sprague-Dawley rats were suspended for isometric tension recording. They were pre-contracted with Phe (10-6 M). Concentration-relaxation response curves to new compounds (10-9-10-4M) was performed at the plateau of contractile response to Phe. The IC50 (concentration necessary for 50% reduction of maximal Phe induced contraction) and maximal response (Emax) achieved for each compound were compared with that of acetylcholine. All compounds were dissolved in dimethylsulfoxide (DMSO) as stock solution (10-9-10-4M) as well as ACh (reference standard). Results: The IC50 of 7-{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}-4-methyl-4a,8adihydro-2H-chromen-2-one , N,N-bis{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methyl}-4-methyl benzene sulfonamide, and (1R)-2-(4-butyl-1H-1,2,3-triazol-1-yl)cyclohexanol were more than that of Ach. The maximal response of 7-{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}-4-methyl-4a,8adihydro-2H-chromen-2-one and (1R)-2-(4-butyl-1H-1,2,3-triazol-1-yl)cyclohexanol were comparable to Ach. Conclusions: The findings of our study revealed that all of the compounds did have vasorelaxing activity on the isolated thoracic rat aorta and they may provide valuable therapeutic intervention for the treatment of hypertension.
Both renal and respiratory diseases are common with high mortality rate around the world. This st... more Both renal and respiratory diseases are common with high mortality rate around the world. This study was the first to compare effects of two kidneys, one clip (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right ventricular pressure during normal condition and mechanical ventilation with hypoxia gas. Male Sprague-Dawley rats were subjected to control, 2K1C, or 1K1C groups. Twenty-eight days after the first surgery, animals were anesthetized, and femoral artery and vein, and right ventricle cannulated. Systemic arterial pressure and right ventricular systolic pressures (RVSP) were recorded during ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was significantly more than the control and 2K1C groups during baseline conditions and ventilation the animals with hypoxic gas. Administration of antioxidant Trolox increased RVSP in the 1K1C and control groups compared with their baselines. Furthermore, there was no alteration in RVSP during hypoxia in the presence of Trolox. This study indicated that RVSP only increased after 28 days induction of 1K1C but not 2K1C model. In addition, it seems that the response to hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest that effects of 1K1C may partially be related to reactive oxygen species (ROS) pathways.
Background: Vascular disease is the principal cause of morbidity and mortality in patients with d... more Background: Vascular disease is the principal cause of morbidity and mortality in patients with diabetes. A considerable body of evidence implicates oxidative stress as an important pathogenic factor of diabetic vasculopathies. In the present study, the effect of hesperidin, a flavanone glycoside with antioxidant activity, is studied in endothelium-dependent relaxation of the rat aorta in experimental diabetes mellitus type 1 (DM1) and type 2 (DM2). Patients and Methods: Single dose intraperitoneal injection of streptozocin (60mg/kg) and subcutaneous daily injection of dexamethasone (10µg/kg for one month) were used to induce DM1 and DM2, respectively. Hesperidin (500mg/kg) was administered orally for two months in DM1 and one month in DM2. The effect of acetylcholine (Ach) on phenyl ephrine (PE) induced. PE contracted aorta was then studied and the EC50 and maximal relaxant effect of Ach were calculated and compared in the two groups.Results: In the experimental DM1, hesperidin res...
Aim: The aim of the present investigation was to elucidate the effects of exercise intensity on ... more Aim: The aim of the present investigation was to elucidate the effects of exercise intensity on exercise‐induced expression of peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) protein in rat skeletal muscle.Methods: We measured PGC‐1α content in the skeletal muscles of male Sprague–Dawley rats (age: 5–6 weeks old; body weight: 150–170 g) after a single session of high‐intensity intermittent exercise (HIE) or low‐intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20‐s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10‐s pause. LIE rats swam with no load for 6 h in two 3‐h sessions, separated by 45 min of rest.Results: After HIE, the PGC‐1α protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age‐matched sedentary control rats’ muscle. Immediately, 6 and 18‐h after LIE, the PGC‐1α protein content in...
Background: Captopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin I... more Background: Captopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin II receptor blocker, are used for the treatment of hypertension, but their effects on cardiac stereology are unknown. This study, therefore, aimed to examine their effects on cardiac stereology in rats with renovascular hypertension. Methods: This study was conducted at Histomorphometry and Stereology Research Centre, and Cardiovascular Pharmacology Research Lab, Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, in August 2015 to August 2016. Fourty-eight rats were allocated to six groups (n=8 per each group): a sham group, which received a vehicle (distilled water) and five renal artery-clipped groups, which received the vehicle, captopril (50 or 100 mg/ kg/day), or losartan (25 or 50 mg/kg/day). After four weeks, the animals’ systolic blood pressures (mm Hg) were measured, and the total volumes of their heart, myocardium, endocardium, m...
Journal of Ardabil University of Medical Sciences, Jun 15, 2014
Background & objectives: Ischemic stroke remains the third leading cause of invalidism and death ... more Background & objectives: Ischemic stroke remains the third leading cause of invalidism and death in industrialized countries. It is suggested that renin-angiotensin system (RAS) may contribute in stroke related pathogenic mechanisms and involve in the ischemic brain damage. This study designed to investigate the role of angiotensin II (Ang II) in conjunction with AT 1 receptors in treatment of the brain injuries following transient focal cerebral ischemia in rats. Methods: Forty eight male Sprague-Dawley rats were studied in four groups. Sham group, ischemic control group and two ischemic groups that received candesartan (0.1mg/kg, or 0.5mg/kg) at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 hours reperfusion. At the end of the reperfusion period, neurological deficit score (NDS) was performed. Total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride (TTC) staining technique. Results: Animals in sham operated group had normal motor function and no ischemic lesions were observed in cortical or striatal regions. Occurring ischemia in ischemic control group that received vehicle produced considerable infarction in cortex (253±15mm 3) and striatum (92±7mm 3), as well as these animals had sever impaired motor dysfunctions. Blocking of AT1 receptors with candesartan (0.1mg/kg or 0.5mg/kg) improved neurological outcome and significantly lowered cortical and striatal infarct volumes relative to ischemic control group. Conclusion: The findings of the present study indicated that stimulation of AT1 receptors by Ang II involved in ischemia/reperfusion injuries and blocking of AT1 receptors can decrease ischemic brain injury and improve neurological outcome.
Summary The objective of this study was to determine the chronology of changes in blood pressure ... more Summary The objective of this study was to determine the chronology of changes in blood pressure in renal hypertension induced by solid plexiglass clips in rats. Saw blades with the thickness of 0.21-0.22 mm were used to make clips sized 4 × 2 × 2 mm from a piece of 2-mm thick plexiglass. Rats were subjected to sham- operation or left renal arterial clipping, and 1, 2, 3 and 4 weeks later blood pressure, and heart and kidneys weights were determined. Relative to those of sham-operated rats, mean blood pressure of left renal artery- clipped rats were significantly higher at week 1 through 4 after clipping. Left renal artery clipping was also associated with significant increases in heart and right kidney weights and significant decrease in left kidney weight. The findings suggest that clipping of left renal artery using solid plexiglass clips resulted in changes in blood pressure, heart and left and right kidneys weights similar to reported changes in hypertension induced by silver c...
Introduction: Graduate (PhD) students in medical sciences, who will form future faculties and inv... more Introduction: Graduate (PhD) students in medical sciences, who will form future faculties and investigators in Iran's Universities of Medical Sciences, are not trained on scientific writing during their training. The present study describes the design, implementation, and evaluation of Principles of Writing Biomedical Research Paper course. Methods: The course, prepared based on an extensive search of the literature and books on writing biomedical research papers, was offered as an elective course to PhD students at Shiraz University of Medical Sciences in the second semester of 2011-2012 academic year. The structure and function of various sections of a paper and publication ethics were discussed in lecture and practical sessions over a period of 12 weeks. The course was then evaluated using a self-designed questionnaire. Results: The majority of students gave the highest score (20) to the content and implementation of all sessions of the course. Moreover, most of them believed...
S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenes... more S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM) or vehicle for 1day (acute) or 7 days (chronic). RT-PCR and ELISA determined S100β mRNA and intra-and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05). Acute and chronic lithium treatments ...
involved in the overall health beneficial effects observed. 2,3 Type 2 diabetes is associated wit... more involved in the overall health beneficial effects observed. 2,3 Type 2 diabetes is associated with impaired insulin release or insulin resistance, impaired glucose, lipid metabolisms, and increased indices of oxidative stress. Recent investigations suggest that PSO may reduce the risk of type 2 diabetes by
Introduction: Development of brain edema following focal cerebral ischemia exacerbates primary is... more Introduction: Development of brain edema following focal cerebral ischemia exacerbates primary ischemic injury. Blood brain
Background: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has ... more Background: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium's neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal and mixed neuron-astrocyte cultures. Methods: Rat primary astrocyte, neuronal, and mixed neuronastrocyte cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and ELISA, respectively. Results: Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied. Conclusion: Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium's action. In light of the evidence showing decreased numbers of glial cells in the post-mortem brain of patients bipolar disorder with and increased glial numbers following lithium treatment, the findings of this study indicate that lithium's action on astrocytes may account, at least in part, for its therapeutic effects in bipolar disorder.
Background: Hawthorn species decreases blood pressure and relaxes precontracted vessels. This stu... more Background: Hawthorn species decreases blood pressure and relaxes precontracted vessels. This study aimed at examining the antihypertensive effect and related mechanisms of hydroalcoholic extract of Crataegus azarolus subspecies aronia fruit in rats with renovascular hypertension. Methods: Six groups of male Sprague-Dawley rats, each containing 6 to 8 rats, were studied. The groups comprised of one sham group and 5 renal artery-clipped groups. The sham group received vehicle (distilled water 0.5 ml/day) and the renal artery-clipped groups received vehicle or the extract at 5, 10, 20 or 30 mg/kg/day. Oral vehicle or extract was administered daily for 4 weeks following sham-operation or induction of hypertension. Systolic blood pressure and heart rate were measured weekly. Isolated aorta study was performed by last week and serum superoxide dismutase and glutathione reductase were measured. The findings were analyzed using one-way analysis of variance and Duncan's multiple range t...
Changes in the substitutions at C-3 and C-5 positions of 4-(1-methyl-5-nitro-2-imidazolyl) dihydr... more Changes in the substitutions at C-3 and C-5 positions of 4-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine have led to changes in potency of the compounds. The objective of the present study was to examine the hypotensive effects of 5 newly synthesized dihydropyridine derivatives of nifedipine in rats with phenylephrine-raised blood pressure. Anesthetized Sprague-Dawley rats were randomly assigned to 19 groups of 7 animals each. Control group received the vehicle dimethylsulfoxide (0.05 mL), 3 groups were given nifedipine at 100, 300, or 1000 g/kg, and 5 other groups each composed of 3 subgroups administered one of the 5 new dihydropyridine compound at 100, 300, or 1000 g/kg. All animals were initially infused with 20 µg/kg/min phenylephrine for 45 min, and were then given a bolus of either dimethylsulfoxide, nifedipine, or new dihydropyridine compounds 20 min after the commencement of phenylephrine infusion. Blood pressure and heart rate (HR) of the animals were measured before and at the end of phenylephrine infusion, or 25 min after injection of vehicle or compounds. Compared to dimethylsulfoxide, nifedipine, and new 1, 4-dihydropyridine derivatives caused significant reductions in MBP. Moreover, cyclohexyl propyl, phenyl butyl, and cyclohexyl methyl analogs of 1, 4-dihydro-2,6-dimethyl-4-(1-methyl-5-nitro-2-imidazoyl)-3,5-pyridinedicarboxylase at 100 g/kg, phenyl butyl, and cyclohexyl methyl analogs at 300 g/kg, and cyclohexyl methyl analogs at 1000 g/kg reduced MBP similar to nifedipine. There was no significant difference between HR of all groups before and after administration of the compounds. The findings indicated that changes in substitution at C-3 and C-5 positions of 2-(1-methyl-5-nitro-2-imidazolyl) dihydropyridine analogs of nifedipine were associated with changes in hypotensive activity of the compounds.
Background: The role of Renin Angiotensin System (RAS) in ischemic/reperfusion (I/R) injuries is ... more Background: The role of Renin Angiotensin System (RAS) in ischemic/reperfusion (I/R) injuries is not fully elucidated. Furthermore, it is not clear whether inhibition of RAS by Angiotensin-Converting Enzyme (ACE) inhibitors has beneficial effects in terms of protecting the brain from I/R injuries. In this study enalapril is used as an ACE inhibitor to evaluate the role of RAS in I/R injuries in the rat. Methods: ACE inhibition was performed one hour before induction of ischemia using a single IP injection of 0.03 mg/kg or 0.1 mg/kg enalapril in the rats. Transient focal cerebral ischemia was induced by 60 min occlusion of the middle cerebral artery followed by reperfusion. Neurological deficit score (NDS) test was performed 24 hours after the start of reperfusion. Finally the animals were sacrificed under deep anesthesia, the brain removed and prepared for the evaluation of cortical and striatal infarction volumes using Triphenyltetrazolium chloride staining method. Results: Pre-ischemic inhibition of ACE with non-hypotensive dose of enalapril (0.03mg/kg) significantly reduced cortical and striatal infarction volumes of ischemic rats by 41.6% and 52.7% respectively with concomitant improvements in NDS. However, no improvement was observed when ACE inhibition accompanied with arterial hypotension. Conclusion: In the rat model of transient focal cerebral ischemia, ACE inhibition seems to reduce the severity of I/R injuries. Therefore, it is plausible to conclude that renin-angiotensinsystem may participate in ischemic/reperfusion injuries.
The first part of this thesis examined the acute cardiovascular effects of CGS 21680, a selective... more The first part of this thesis examined the acute cardiovascular effects of CGS 21680, a selective adenosine A 2 A receptor agonist, relative to those of sodium nitroprusside (SNP) and vehicle (normal saline) in male Sprague-Dawley rats with or without acute occlusion or chronic ligation of the left main coronary artery. Rats with chronic coronary ligation were studied 8 weeks after the operation. The second part examined the chronic effects of 17(3-estradiol, the most abundant naturally-occurring estrogen, relative to those of vehicle on in vivo cardiovascular function and response to vasoactive drugs in ovariectomised rats at 7 weeks after ligation of the left coronary artery. It also; examined the effects of 17(3-estradiol on ex vivo contractile and relaxant responses of aortic rings, pulmonary artery rings and portal vein strips to vasoactive drugs. The ovariectomised rats were implanted with 60 days sustained-release pellets containing 17(3-estradiol (1.5 mg) or vehicle one week...
Background and Aims: Triazole derivatives are widely used as anticancer, antituberculosis, antifu... more Background and Aims: Triazole derivatives are widely used as anticancer, antituberculosis, antifungal, antibacterial, and anti-HIV. The present study compared the vasorelaxing activities of 12 triazoles, which were synthesized via an expedient method, with that of acetylcholine (Ach) using rat aortic rings. Methods: Synthesis of β-Hydroxy 1,4-Disubstituted-1,2,3-triazole Derivatives. Epoxide/benzyl bromide (1 mmol), alkyne (1 mmol) and sodium azide (1.1 mmol) were mixed and stirred in water in the presence of the naocatalyst (2 mol %) at room temperature. After the completion of the reaction, the mixture was vacuumfiltered and washed with ethyl acetate. The organic layer was dried over anhydrous Na2SO4. Removal of the solvent under vacuum, followed by purification on silica gel column afforded the pure products. Preparation of the rat aorta. Thoracic aortic rings from 6 normal Sprague-Dawley rats were suspended for isometric tension recording. They were pre-contracted with Phe (10-6 M). Concentration-relaxation response curves to new compounds (10-9-10-4M) was performed at the plateau of contractile response to Phe. The IC50 (concentration necessary for 50% reduction of maximal Phe induced contraction) and maximal response (Emax) achieved for each compound were compared with that of acetylcholine. All compounds were dissolved in dimethylsulfoxide (DMSO) as stock solution (10-9-10-4M) as well as ACh (reference standard). Results: The IC50 of 7-{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}-4-methyl-4a,8adihydro-2H-chromen-2-one , N,N-bis{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methyl}-4-methyl benzene sulfonamide, and (1R)-2-(4-butyl-1H-1,2,3-triazol-1-yl)cyclohexanol were more than that of Ach. The maximal response of 7-{[1-(2-hydroxy-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methoxy}-4-methyl-4a,8adihydro-2H-chromen-2-one and (1R)-2-(4-butyl-1H-1,2,3-triazol-1-yl)cyclohexanol were comparable to Ach. Conclusions: The findings of our study revealed that all of the compounds did have vasorelaxing activity on the isolated thoracic rat aorta and they may provide valuable therapeutic intervention for the treatment of hypertension.
Both renal and respiratory diseases are common with high mortality rate around the world. This st... more Both renal and respiratory diseases are common with high mortality rate around the world. This study was the first to compare effects of two kidneys, one clip (2K1C) and one-kidney, one clip (1K1C) Goldblatt hypertension on right ventricular pressure during normal condition and mechanical ventilation with hypoxia gas. Male Sprague-Dawley rats were subjected to control, 2K1C, or 1K1C groups. Twenty-eight days after the first surgery, animals were anesthetized, and femoral artery and vein, and right ventricle cannulated. Systemic arterial pressure and right ventricular systolic pressures (RVSP) were recorded during ventilation the animals with normoxic or hypoxic gas. RVSP in the 1K1C group was significantly more than the control and 2K1C groups during baseline conditions and ventilation the animals with hypoxic gas. Administration of antioxidant Trolox increased RVSP in the 1K1C and control groups compared with their baselines. Furthermore, there was no alteration in RVSP during hypoxia in the presence of Trolox. This study indicated that RVSP only increased after 28 days induction of 1K1C but not 2K1C model. In addition, it seems that the response to hypoxic gas and antioxidants in 1K1C is more than 2K1C. These data also suggest that effects of 1K1C may partially be related to reactive oxygen species (ROS) pathways.
Background: Vascular disease is the principal cause of morbidity and mortality in patients with d... more Background: Vascular disease is the principal cause of morbidity and mortality in patients with diabetes. A considerable body of evidence implicates oxidative stress as an important pathogenic factor of diabetic vasculopathies. In the present study, the effect of hesperidin, a flavanone glycoside with antioxidant activity, is studied in endothelium-dependent relaxation of the rat aorta in experimental diabetes mellitus type 1 (DM1) and type 2 (DM2). Patients and Methods: Single dose intraperitoneal injection of streptozocin (60mg/kg) and subcutaneous daily injection of dexamethasone (10µg/kg for one month) were used to induce DM1 and DM2, respectively. Hesperidin (500mg/kg) was administered orally for two months in DM1 and one month in DM2. The effect of acetylcholine (Ach) on phenyl ephrine (PE) induced. PE contracted aorta was then studied and the EC50 and maximal relaxant effect of Ach were calculated and compared in the two groups.Results: In the experimental DM1, hesperidin res...
Aim: The aim of the present investigation was to elucidate the effects of exercise intensity on ... more Aim: The aim of the present investigation was to elucidate the effects of exercise intensity on exercise‐induced expression of peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) protein in rat skeletal muscle.Methods: We measured PGC‐1α content in the skeletal muscles of male Sprague–Dawley rats (age: 5–6 weeks old; body weight: 150–170 g) after a single session of high‐intensity intermittent exercise (HIE) or low‐intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20‐s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10‐s pause. LIE rats swam with no load for 6 h in two 3‐h sessions, separated by 45 min of rest.Results: After HIE, the PGC‐1α protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age‐matched sedentary control rats’ muscle. Immediately, 6 and 18‐h after LIE, the PGC‐1α protein content in...
Background: Captopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin I... more Background: Captopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin II receptor blocker, are used for the treatment of hypertension, but their effects on cardiac stereology are unknown. This study, therefore, aimed to examine their effects on cardiac stereology in rats with renovascular hypertension. Methods: This study was conducted at Histomorphometry and Stereology Research Centre, and Cardiovascular Pharmacology Research Lab, Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, in August 2015 to August 2016. Fourty-eight rats were allocated to six groups (n=8 per each group): a sham group, which received a vehicle (distilled water) and five renal artery-clipped groups, which received the vehicle, captopril (50 or 100 mg/ kg/day), or losartan (25 or 50 mg/kg/day). After four weeks, the animals’ systolic blood pressures (mm Hg) were measured, and the total volumes of their heart, myocardium, endocardium, m...
Journal of Ardabil University of Medical Sciences, Jun 15, 2014
Background & objectives: Ischemic stroke remains the third leading cause of invalidism and death ... more Background & objectives: Ischemic stroke remains the third leading cause of invalidism and death in industrialized countries. It is suggested that renin-angiotensin system (RAS) may contribute in stroke related pathogenic mechanisms and involve in the ischemic brain damage. This study designed to investigate the role of angiotensin II (Ang II) in conjunction with AT 1 receptors in treatment of the brain injuries following transient focal cerebral ischemia in rats. Methods: Forty eight male Sprague-Dawley rats were studied in four groups. Sham group, ischemic control group and two ischemic groups that received candesartan (0.1mg/kg, or 0.5mg/kg) at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 hours reperfusion. At the end of the reperfusion period, neurological deficit score (NDS) was performed. Total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride (TTC) staining technique. Results: Animals in sham operated group had normal motor function and no ischemic lesions were observed in cortical or striatal regions. Occurring ischemia in ischemic control group that received vehicle produced considerable infarction in cortex (253±15mm 3) and striatum (92±7mm 3), as well as these animals had sever impaired motor dysfunctions. Blocking of AT1 receptors with candesartan (0.1mg/kg or 0.5mg/kg) improved neurological outcome and significantly lowered cortical and striatal infarct volumes relative to ischemic control group. Conclusion: The findings of the present study indicated that stimulation of AT1 receptors by Ang II involved in ischemia/reperfusion injuries and blocking of AT1 receptors can decrease ischemic brain injury and improve neurological outcome.
Summary The objective of this study was to determine the chronology of changes in blood pressure ... more Summary The objective of this study was to determine the chronology of changes in blood pressure in renal hypertension induced by solid plexiglass clips in rats. Saw blades with the thickness of 0.21-0.22 mm were used to make clips sized 4 × 2 × 2 mm from a piece of 2-mm thick plexiglass. Rats were subjected to sham- operation or left renal arterial clipping, and 1, 2, 3 and 4 weeks later blood pressure, and heart and kidneys weights were determined. Relative to those of sham-operated rats, mean blood pressure of left renal artery- clipped rats were significantly higher at week 1 through 4 after clipping. Left renal artery clipping was also associated with significant increases in heart and right kidney weights and significant decrease in left kidney weight. The findings suggest that clipping of left renal artery using solid plexiglass clips resulted in changes in blood pressure, heart and left and right kidneys weights similar to reported changes in hypertension induced by silver c...
Introduction: Graduate (PhD) students in medical sciences, who will form future faculties and inv... more Introduction: Graduate (PhD) students in medical sciences, who will form future faculties and investigators in Iran's Universities of Medical Sciences, are not trained on scientific writing during their training. The present study describes the design, implementation, and evaluation of Principles of Writing Biomedical Research Paper course. Methods: The course, prepared based on an extensive search of the literature and books on writing biomedical research papers, was offered as an elective course to PhD students at Shiraz University of Medical Sciences in the second semester of 2011-2012 academic year. The structure and function of various sections of a paper and publication ethics were discussed in lecture and practical sessions over a period of 12 weeks. The course was then evaluated using a self-designed questionnaire. Results: The majority of students gave the highest score (20) to the content and implementation of all sessions of the course. Moreover, most of them believed...
S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenes... more S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM) or vehicle for 1day (acute) or 7 days (chronic). RT-PCR and ELISA determined S100β mRNA and intra-and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05). Acute and chronic lithium treatments ...
involved in the overall health beneficial effects observed. 2,3 Type 2 diabetes is associated wit... more involved in the overall health beneficial effects observed. 2,3 Type 2 diabetes is associated with impaired insulin release or insulin resistance, impaired glucose, lipid metabolisms, and increased indices of oxidative stress. Recent investigations suggest that PSO may reduce the risk of type 2 diabetes by
Introduction: Development of brain edema following focal cerebral ischemia exacerbates primary is... more Introduction: Development of brain edema following focal cerebral ischemia exacerbates primary ischemic injury. Blood brain
Background: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has ... more Background: B cell CLL/lymphoma 2 protein, bcl-2, is an important anti-apoptotic factor that has been implicated in lithium's neuroprotective effect. However, most studies have focused on assessing the effects of lithium in neurons, ignoring examination of bcl-2 in astrocytes, which also influence neuronal survival and are affected in bipolar disorder. The aim of this study was to evaluate whether chronic lithium treatment also elevates bcl-2 expression in astrocytes compared with neuronal and mixed neuron-astrocyte cultures. Methods: Rat primary astrocyte, neuronal, and mixed neuronastrocyte cultures were prepared from the cerebral cortices of 18-day embryos. The cell cultures were treated with lithium (1 mM) or vehicle for 24 h or 7 days. Thereafter, bcl-2 mRNA and protein levels were determined by RT-PCR and ELISA, respectively. Results: Chronic, but not acute, lithium treatment significantly increased bcl-2 protein levels in the astrocyte cultures compared with the vehicle-treated cultures. While lithium treatment increased bcl-2 protein levels in both neuronal and mixed neuron-astrocyte cultures, the elevations fell short of statistical significance compared with the respective vehicle-treated cultures. However, neither acute nor chronic lithium treatment affected bcl-2 mRNA levels in any of the three cell types studied. Conclusion: Increased bcl-2 levels in rat primary astrocyte cultures following chronic lithium treatment suggest astrocytes are also a target of lithium's action. In light of the evidence showing decreased numbers of glial cells in the post-mortem brain of patients bipolar disorder with and increased glial numbers following lithium treatment, the findings of this study indicate that lithium's action on astrocytes may account, at least in part, for its therapeutic effects in bipolar disorder.
Background: Hawthorn species decreases blood pressure and relaxes precontracted vessels. This stu... more Background: Hawthorn species decreases blood pressure and relaxes precontracted vessels. This study aimed at examining the antihypertensive effect and related mechanisms of hydroalcoholic extract of Crataegus azarolus subspecies aronia fruit in rats with renovascular hypertension. Methods: Six groups of male Sprague-Dawley rats, each containing 6 to 8 rats, were studied. The groups comprised of one sham group and 5 renal artery-clipped groups. The sham group received vehicle (distilled water 0.5 ml/day) and the renal artery-clipped groups received vehicle or the extract at 5, 10, 20 or 30 mg/kg/day. Oral vehicle or extract was administered daily for 4 weeks following sham-operation or induction of hypertension. Systolic blood pressure and heart rate were measured weekly. Isolated aorta study was performed by last week and serum superoxide dismutase and glutathione reductase were measured. The findings were analyzed using one-way analysis of variance and Duncan's multiple range t...
Uploads
Papers by Ali nekooeian