Papers by Sulayma Albarwani
The Journal of Physiology, 1993
Research Square (Research Square), Feb 14, 2022
Background: Serum creatinine and estimated glomerular ltration rate (eGFR) are keys to assess kid... more Background: Serum creatinine and estimated glomerular ltration rate (eGFR) are keys to assess kidney function and suggest a propensity for development of renal failure. Genetic factors are reported in different ethnic groups to play a role in the variability of these phenotypes. In this study, we investigate the heritability and quantitative trait loci (QTL) of serum creatinine and eGFR. Multiple phenotypes were collected from a multi-generation pedigree of 281 subjects form Oman family study. Genotype analysis was used to calculate heritability and linkage was performed using variance components decompositionbased methods implemented in SOLAR. Results: The multivariate-adjusted heritability estimates for serum creatinine and eGFR were 0.70 and 0.63 (p-value 2.5x10-11 and 1.8x10-11), respectively. Genome-wide linkage analysis showed signi cant loci with LOD score ≥2 at chromosomes 9p21.1, 9p21.3, 15p26.3 and 16.p13.3. Functional annotation identi ed angiopoietin 1-TEK pathway as a candidate pathway where TEK is associated with chronic kidney disease and expressed in renal glomeruli. Conclusion: This study showed high heritability of serum creatinine and eGFR with signi cant QTLs in chromosomes 9, 15 and 16. Further research is needed to study the genetic association studies of angiopoietin 1-TEK axis with glomerulopathies like type 2 diabetes and to predict and diagnose progression of renal diseases.
Biochemical and Biophysical Research Communications, Sep 1, 1999
We have, for the first time, developed a reliable method for freshly isolating viable endothelial... more We have, for the first time, developed a reliable method for freshly isolating viable endothelial cells from resistance-sized rat pulmonary arteries. The endothelial origin of these cells was confirmed using indirect immunofluorescence, utilizing fluorescently labeled low-density lipoprotein. Biophysical and pharmacological patch-clamp experiments conducted under quasiphysiological cationic gradients revealed that these cells had a mean resting membrane potential of ϳ؊38 mV and displayed a delayed-rectifying K ؉ current. Immunohistochemical staining of rat lung cross-sections revealed an abundance of K V 1.5 channel protein in pulmonary endothelium. This is the first report of a delayed-rectifying K ؉ current in endothelial cells of resistance-sized pulmonary arteries. Since changes in membrane potential associated with K ؉ channel activity affect release of vasoactive substances from endothelial cells, this finding has important implications for understanding the mechanisms underlying control of pulmonary vascular tone.
Experimental Physiology, Sep 1, 1995
Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1; 0.8-16nM) enhance... more Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1; 0.8-16nM) enhanced a voltage-activated outward current ('out) and induced periodic oscillations of inward current in smooth muscle cells isolated from small pulmonary arteries (200-400 ,um in diameter). Anion substitution experiments revealed that the ET-1-induced inward current was carried by Clions. Application of bosentan (10 #m; an ETA and ETB receptor antagonist) and FR 139317 (1-10 uM; a selective ETA receptor antagonist) prevented initiation of inward currents or enhancement of Iout by ET-1. The ETB receptor agonist tetra-Ala-endothelin-1 (1-20 nM) failed to evoke these responses. Caffeine (10 mM) induced a single transient inward current and prevented any further activation of inward current, or enhancement of Iout, by subsequent application of 16 nm ET-1, suggesting that these currents were mediated by Ca2' release from internal stores. Rapid intracellular release of Ca2' by photolysis of nitr-5 activated an inward Clcurrent and increased the magnitude of Iout These results demonstrate the existence of Ca2+_ activated Cland K+ channels in pulmonary arterial smooth muscle. The physiological role of these channels is at present uncertain, although their activation may be involved in the contractile responses of pulmonary arterial smooth muscle to ET-1.
Physiological Research, Mar 22, 2022
Exercise training (ET) is well established to induce vascular adaptations on the metabolically ac... more Exercise training (ET) is well established to induce vascular adaptations on the metabolically active muscles. These adaptations include increased function of vascular potassium channels and enhanced endothelium-dependent relaxations. However, the available data on the effect of ET on vasculatures that normally constrict during exercise, such as mesenteric arteries (MA), are scarce and not conclusive. Therefore, this study hypothesized that 10 weeks of moderate-intensity ET would result in adaptations towards more vasoconstriction or/and less vasodilatation of MA. Young Fischer 344 rats were randomly assigned to a sedentary group (SED; n=24) or exercise training group (EXE; n=28). The EXE rats underwent a progressive treadmill ET program for 10 weeks. Isometric tensions of small (SED; 252.9±29.5 µm, EXE; 248.6±34.4 µm) and large (SED; 397.7±85.3 µm, EXE; 414.0±86.95 µm) MA were recorded in response to cumulative phenylephrine concentrations (PE; 0-30 µM) in the presence and absence of the BK Ca channel blocker, Iberiotoxin (100 nM). In another set of experiments, tensions in response to cumulative concentration-response curves of acetylcholine (ACh) or sodium nitroprusside (SNP) were obtained, and pEC50s were compared. Immunoblotting was performed to measure protein expression levels of the BKCa channel subunits and eNOS. ET did not alter the basal tension of small and large MA but significantly increased their responses to PE, and reduced the effect of BKCa channels in opposing the contractile responses to PE without changes in the protein expression level of BKCa subunits. ET also elicited a sizedependent functional adaptations that involved reduced endothelium-independent and endothelium-dependent relaxations. In large MA the sensitivity to SNP was decreased more than in small MA suggesting impaired nitric oxide (NO)-dependent mechanisms within the vascular smooth muscle cells of ET group. Whereas the shift in pEC50 of ACh-induced relaxation of small MA would suggest more effect on the production of NO within the endothelium, which is not changed in large MA of ET group. However, the eNOS protein expression level was not significantly changed between the ET and SED groups. In conclusion, our results indicate an increase in contraction and reduced relaxation of MA after 10 weeks of ET, an adaptation that may help shunt blood flow to metabolically active tissues during acute exercise.
Physiological Research, 2022
Exercise training (ET) is well established to induce vascular adaptations on the metabolically ac... more Exercise training (ET) is well established to induce vascular adaptations on the metabolically active muscles. These adaptations include increased function of vascular potassium channels and enhanced endothelium-dependent relaxations. However, the available data on the effect of ET on vasculatures that normally constrict during exercise, such as mesenteric arteries (MA), are scarce and not conclusive. Therefore, this study hypothesized that 10 weeks of moderate-intensity ET would result in adaptations towards more vasoconstriction or/and less vasodilatation of MA. Young Fischer 344 rats were randomly assigned to a sedentary group (SED; n=24) or exercise training group (EXE; n=28). The EXE rats underwent a progressive treadmill ET program for 10 weeks. Isometric tensions of small (SED; 252.9±29.5 µm, EXE; 248.6±34.4 µm) and large (SED; 397.7±85.3 µm, EXE; 414.0±86.95 µm) MA were recorded in response to cumulative phenylephrine concentrations (PE; 0-30 µM) in the presence and absence ...
Physiological Research, 2015
Pathogenesis of adenine-induced chronic renal failure may involve inflammatory, immunological and... more Pathogenesis of adenine-induced chronic renal failure may involve inflammatory, immunological and/or oxidant mechanisms. Gum arabic (GA) is a complex polysaccharide that acts as an anti-oxidant which can modulate inflammatory and/or immunological processes. Therefore, we tested here the effect of GA treatment (15 % in the drinking water for 4 weeks) in plasma and urine of rats, on a novel cytokine that has been shown to be pro-inflammatory, viz, DNA-binding high-mobility group box-1 protein (HMGB1). Adenine (0.75 % in the feed, 4 weeks) significantly increased indoxyl sulphate, urea and creatinine concentrations in plasma, and significantly decreased the creatinine clearance. GA significantly abated these effects. The concentrations of HMGB1 in urine before the start of the experiment were similar in all four groups. However, 24 h after the last treatment, adenine treatment increased significantly the concentration of HMGB1 when compared with the control. GA treatment did not affect...
Scientific Reports, 2019
This family study from Oman (n = 1231) explored the heritability and genetic and environmental co... more This family study from Oman (n = 1231) explored the heritability and genetic and environmental correlations of heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS) with ambulatory and beat-to-beat blood pressure (BP). Ambulatory BP was measured for 24 hours to calculate mean values for daytime and sleep separately. Time and frequency domain HRV indices, BRS, office beat-to-beat BP, and heart rate (HR) were measured for 10 minutes at rest. SOLAR software was used to perform univariate and bivariate quantitative genetic analyses adjusting for age, age2, sex, their interactions and BMI. Heritability of SBP and DBP ranged from 16.8% to 40.4% for daytime, sleeping, 24-hour and office beat-to-beat measurements. HR and BRS showed a heritability of 31.9% and 20.6%, respectively, and for HRV indices heritability ranged from 11.1% to 20.5%. All HRV measurements and BRS were found to be negatively correlated with BP, but phenotypic correlation coefficients were relatively wea...
Journal of Obesity and Overweight, 2016
Obesity is a known risk for cardio-metabolic diseases such as hypertension, ischemic heart diseas... more Obesity is a known risk for cardio-metabolic diseases such as hypertension, ischemic heart disease [1,2], type-2 diabetes mellitus [3] and comorbidities like obstructive sleep apnea [4]. Previous studies showed hemodynamic and autonomic alterations in lean compared to obese [5,6] such as increased resting heart rate (HR), blood pressure (BP) [5,7], muscle sympathetic nerve activity (MSNA) [5,7,8], left ventricular mass index [9] and low frequency spectrum of heart rate variability (HRV) [6]. Contrary to this, autonomic activity was also shown to decrease with obesity [10,11] and had inverse relationship with body fat percentage [1].
Experimental Physiology, 1995
Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1; 0.8-16nM) enhance... more Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1; 0.8-16nM) enhanced a voltage-activated outward current ('out) and induced periodic oscillations of inward current in smooth muscle cells isolated from small pulmonary arteries (200-400 ,um in diameter). Anion substitution experiments revealed that the ET-1-induced inward current was carried by Clions. Application of bosentan (10 #m; an ETA and ETB receptor antagonist) and FR 139317 (1-10 uM; a selective ETA receptor antagonist) prevented initiation of inward currents or enhancement of Iout by ET-1. The ETB receptor agonist tetra-Ala-endothelin-1 (1-20 nM) failed to evoke these responses. Caffeine (10 mM) induced a single transient inward current and prevented any further activation of inward current, or enhancement of Iout, by subsequent application of 16 nm ET-1, suggesting that these currents were mediated by Ca2' release from internal stores. Rapid intracellular release of Ca2' by photolysis of nitr-5 activated an inward Clcurrent and increased the magnitude of Iout These results demonstrate the existence of Ca2+_ activated Cland K+ channels in pulmonary arterial smooth muscle. The physiological role of these channels is at present uncertain, although their activation may be involved in the contractile responses of pulmonary arterial smooth muscle to ET-1.
Ion Flux in Pulmonary Vascular Control, 1993
Pulmonary vascular smooth muscle and the carotid body chemoreceptors are both excited by hypoxia,... more Pulmonary vascular smooth muscle and the carotid body chemoreceptors are both excited by hypoxia, but our understanding of the mechanism responsible for excitation of the former has lagged behind, and this is largely because the muscle cells have only recently been studied using patch (Post et al., 1992; Robertson et al., 1992a) and fluorescence (Robertson et al., 1993b) techniques. It seems to us that, just as the carotid body field is being advanced rapidly by the performance of experiments on single cells, and relating the results from these to more traditional work on the discharge of chemoreceptors, so experiments on single smooth muscle cells from pulmonary vessels, backed up by complementary experiments on isolated vessels and lungs, are likely to be the most successful way forward.
The Journal of Physiology, 2003
Recently, efforts have intensified to identify the types of voltage-gated K + (K V) channels in t... more Recently, efforts have intensified to identify the types of voltage-gated K + (K V) channels in the cerebral circulation based on findings that vascular smooth muscle cells (VSMCs) rely on K V channels for vasodilatation (Cheong et al. 2001a,b). Several studies have demonstrated that K V channels contribute to the resting membrane potential (V m) and diameter of cerebral microvessels, and that pharmacological inhibition of these channels depolarizes and constricts small cerebral arteries and arterioles, both in vitro and in vivo (Knot & Nelson, 1995; Sobey & Faraci, 1999; Horuichi et al. 2001). Strong evidence also indicates that K V channels in VSMCs are regulated by intracellular calcium, intravascular pressure and vasoconstrictor agents (Knot & Nelson, 1995; Faraci & Heistad, 1998; Cox & Petrou, 1999), and alterations in these factors have been implicated in pathological conditions including cerebral vasospasm and stroke (Faraci & Heistad, 1998). Thus, identifying the molecular composition of the functionally significant K V channels in the cerebral circulation has immediate implications for determining the ionic mechanisms that regulate blood flow to the brain. Unfortunately, efforts to identify the composition of K V channels have been hampered by the highly diverse nature of K V channels, whose pore-forming a-subunits arise from at least 11 different gene families (K V 1-K V 11), each composed of several subfamily members (Coetzee et al. 1999; Robertson, 2001; Ottschytsch et al. 2002). Four similar or different a-subunits emanating from a single gene assemble as homo-or heterotetramers, respectively, to form the K +-selective pore. Many channels show overlap in their properties of unitary conductance, voltage-dependent activation and inactivation, and sensitivity to pharmacological antagonists (Coetzee et al. 1999; Robertson, 2001). For example, 4-aminopyridine (4-AP), the classical pharmacological antagonist of K V channels, shows only about a 10-fold difference in blocking potency between most K V gene families. Much is known about its blocking actions on cloned K V channel
Pfl�gers Archiv European Journal of Physiology, 1994
A novel class of Ca2+-activated K + channel, also activated by Mg-ATR exists in the main pulmonar... more A novel class of Ca2+-activated K + channel, also activated by Mg-ATR exists in the main pulmonary artery of the rat. In view of the sensitivity of these "Kca,ATp" channels to such charged intermediates it is possible that they may be involved in regulating cellular responses to hypoxia. However, their electrophysiologicat profile is at present unknown. We have therefore characterised the sensitivity of KCa,ATe channels to voltage, intracellular Ca 2+ ([Ca2+]i) and Mg-ATR They have a conductance of 245 pS in symmetrical K + and are approximately 20 times more selective for K § ions than Na + ions, with a K + permeability (PrO of 4.6• s-1. Ca 2+ ions applied to the intracellular membrane surface of KCa,ATP channels causes a marked enhancement of their activity. This activation is probably the result of simultaneous binding of at least two Ca 2+ ions, determined using Hill analysis, to the channel or some closely associated protein. This results in a shift of the voltage activation threshold to more hyperpolarized membrane potentials. The activation of KCa.AT~, channels by Mg-ATP has an ECso of approximately 50 laM. Although the ECso is unaffected by [Ca2+]~, channel activation by Mg-ATP is enhanced by increasing [Ca2+]~. One possible interpretation of these data is that Mg-ATP increases the sensitivity of Kca,A~ channels to Ca 2+. It is therefore possible that under hypoxic conditions, where lower levels of Mg-ATP may be encountered, the sensitivity of Kca,ATe channels to Ca 2+ and therefore voltage is reduced. This would tend to induce a depolarising influence, which would favour the influx of Ca 2+ through voltage-activated Ca 2 § channels, ultimately leading to increased vascular tone.
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Papers by Sulayma Albarwani