Papers by Hendrik Buikema
The Canadian journal of cardiology, 2003
CONTEXTS: Les patients porteurs du génotype de délétion de l'enzyme de conversion de l'... more CONTEXTS: Les patients porteurs du génotype de délétion de l'enzyme de conversion de l'angiotensine(ECA) auraient one réaction de croissance cardiovasculaire plus prononcée après certaines interventions cardiovasculaires, ce qui pourrait expliquer l'effet de l' ...
Nephron Physiology, 2005
Cardiovascular disease is a major cause of death following renal transplantation. Mechanisms lead... more Cardiovascular disease is a major cause of death following renal transplantation. Mechanisms leading to vascular dysfunction outside the transplanted organ involve common risk factors such as hypertension, hypercholesterolemia, proteinuria, but immune-mediated factors may also be involved. We hypothesized that transplantation-associated risk factors are involved in the development of vascular dysfunction following renal transplantation. Vascular function was studied in Fisher to Lewis allografts. Lewis to Lewis syngrafted rats served as controls. All rats received cyclosporin A for 10 days. Allografts were treated with ACE inhibition or AT1 receptor blockade or left untreated. After 34 weeks, aorta rings were studied for contractile and dilator responses in the presence or absence of L-NMMA and/or indomethacin. Tissue sections were immunostained for COX-1 and COX-2. In contrast to syngrafts and treated allografts, untreated allografts developed proteinuria and hypercholesterolemia. In aortic rings, NOS inhibition similarly increased contractile responses and decreased dilator responses in syngrafts and allografts, indicating comparable NO pathways. In contrast, indomethacin affected contractile and dilator responses in syngrafts, but not in treated and untreated allografts, indicating absence of COX-derived prostanoids in control over vascular tone in allografts. This was in line with immunohistologic analysis demonstrating reduced aortic COX-2 expression in allografts. COX-1 expression was unaltered. Interestingly, RAS blockade quantitatively increased endothelium-dependent dilation without qualitatively altering COX function and expression. Involvement of COX-derived prostaglandins in vascular endothelial function outside the transplanted organ is strongly diminished after allogeneic renal transplantation. RAS blockade improves common cardiovascular risk factors and endothelium-dependent dilation, but fails to restore prostaglandin function.
Journal of Pharmacology and Experimental Therapeutics, 2004
Low dietary sodium (LS) increases the effect of angiotensin-converting enzyme (ACE) inhibitor the... more Low dietary sodium (LS) increases the effect of angiotensin-converting enzyme (ACE) inhibitor therapy in patients and experimental models, but mechanisms underlying this enhanced efficacy are largely unknown. Because the benefits of ACE inhibition are mediated to a considerable extent by their effect on the vasculature, we studied whether low sodium alters the vascular effects of ACE inhibition. Baseline functional and morphological characteristics, and endothelium-dependent and -independent dilatory responses were studied in isolated perfused small intrarenal and mesenteric arteries obtained from control rats (CON), rats on LS, lisinopril-treated rats (CON-LIS), or rats treated with lisinopril during LS (LS-LIS). We found, first, that LS-LIS compared with CON-LIS enhances blood pressure reduction. Second, interlobar renal arteries had increased lumen diameter and reduced adrenergic contractility in CON-LIS compared with CON, without additional effects of LS. In contrast, mesenteric arteries were not altered in CON-LIS compared with CON, but became triggered for increased myogenic and adrenergic constriction in LS-LIS. Third, LS-LIS decreased acetylcholine (ACh)-induced vasodilation in both mesenteric and renal arteries compared with CON-LIS. During the latter condition, opposite prostaglandins are involved in the endothelial function of the two different vascular beds, i.e., increased involvement of contractile prostaglandins in ACh-induced vasodilatation in renal arteries, versus dilatory prostaglandins in mesenteric arteries. Whether cause or consequence of the enhanced blood pressure response, our data demonstrate a modifying effect of dietary sodium on vascular effects of ACE inhibition. These findings provide a rationale for further studies addressing the mechanism-of-actions of our therapies to find additional strategies to improve therapy response.
Journal of Hypertension, 2005
The classical studies carried out for the first time, some 25 years ago, by Furchgott and Zawadzk... more The classical studies carried out for the first time, some 25 years ago, by Furchgott and Zawadzki [1] demonstrated the obligatory involvement of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine (ACh). Numerous studies thereafter have not only confirmed the role of the endothelium in the (physiological) control of vascular tone, but have also demonstrated impairments in endothelium-dependent relaxation in hypertension and other pathophysiological conditions. From this, the concept of endothelial dysfunction underlying and contributing to cardiovascular disease has subsequently emerged. We are now aware of the crucial role of endothelial function in controlling a broad range of processes guarding vascular integrity (e.g. vascular tone, growth, permeability, inflammation, thrombotic processes, platelet function, etc.), as well as its detrimental role in the derailment of these processes, leading to the development of vasculopathies (including those defining hypertension, atherosclerosis and restenosis after angioplasty). Presently, the essential role of this organ in cardiovascular health and as a therapeutic target of clinical importance is widely acknowledged .
Journal of Hypertension, 2003
Journal of Cardiovascular Pharmacology, 2003
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Expert Review of Cardiovascular Therapy, 2006
Zofenopril, an inhibitor of the angiotensin-converting enzyme (ACE), has recently been widely int... more Zofenopril, an inhibitor of the angiotensin-converting enzyme (ACE), has recently been widely introduced into the pharmaceutical market. Its clinical safety and efficacy has been demonstrated in patients with hypertension and in patients with acute myocardial infarction (AMI). The Survival of Myocardial Infarction Long-term Evaluation (SMILE) project provided valuable information regarding the safety of early onset ACE inhibition with zofenopril after AMI and a greater perception of the early and late benefits. The SMILE-I study demonstrated that most benefits of ACE inhibition may be obtained early after AMI and persist after discontinuation of treatment. The SMILE-II study demonstrated that early zofenopril treatment (initiated <12 h) is safe and associated with a low rate of severe hypotension in thrombolyzed patients with acute myocardial infarction when administered in accordance with an adequate dose-titration scheme. Many other studies of clinical ACE-inhibitors (ACEIs) over the last 30 years have provided us with information in order to understand the effects of ACEIs and have demonstrated that patients benefit from ACEI treatment at different stages of the pathophysiological continuum of cardiovascular diseases. The current guidelines recommend that ACEIs should be used for routine secondary prevention in all patients with coronary artery disease and should be considered for all other patients with coronary or other vascular disease unless contraindicated.
Current Opinion in Pharmacology, 2009
Nephrosis refers to a condition resulting from proteinuric kidney disease, leading to irreversibl... more Nephrosis refers to a condition resulting from proteinuric kidney disease, leading to irreversible renal parenchymal damage and end-stage renal disease when left untreated. Furthermore, nephrosis appears to be a communicable disease carrying risks and complications to other organs such as the heart. Key pathophysiolgical processes involved in initiating and progressing renal damage in nephrosis and its complications may include altered glomerular hemodynamics after initial renal damage and loss of nephrons, nephrotoxicity of increased renal protein traffic enforcing intrinsic 'common pathway' mechanisms of renal scarring, and generalized endothelial dysfunction proceeding CV disease. The reader is first provided a basic overview on key mechanisms, targets and therapies in nephrosis while referred to some excellent updates hereon for more detailed information. The broader purpose of this short review, however, is to highlight caveolae/caveolins and caveolar function as central modulators in all the above key processes of nephrosis. Caveolae - little caves in the plasma membrane that are particularly abundant in endothelial cells, amongst others - are now known to be involved not only in endothelial transcytosis (e.g. of albumin) but also in cholesterol homeostasis (LDL-transport) and, importantly, in signal transduction such as insulin signalling and nitric oxide signalling in endothelial function and regulation of vasomotor tone, as well as signalling by growth factor receptors - such as TGF-beta - which may participate in renal scarring. It is suggested that caveolae may represent crucial sites where possible new druggable targets in nephrosis may be found.
Cardiovascular Drugs and Therapy, 2004
Although Selective Serotonin Reuptake Inhibitors (SSRIs) are important antidepressant drugs, know... more Although Selective Serotonin Reuptake Inhibitors (SSRIs) are important antidepressant drugs, knowledge of their vaso active effects is limited. Vaso active effects of the SSRI sertraline were studied in rings of rat aorta, human Internal Mammary Arteries (IMAs) and in Langendorff perfused rat hearts. The effects of sertraline (0.1 to 300 micromol x L(-1)) on precontracted rat aortic and IMA rings were evaluated in organ bath chambers. Precontraction was elicited by serotonin (5-HT; 10 micromol x L(-1)), phenylephrine (PE; 10 micromol x L(-1)) and potassium chloride (KCl; 50 mmol x L(-1)). In addition, the effects of sertraline on PE induced contraction curves were established by subjecting vascular rings to increasing doses of PE (1 nmol x L(-1) to 10 (micro)mol x L(-1)) in the presence of sertraline or vehicle. Finally, the effects of sertraline on ex vivo coronary flow in rat hearts were examined using a retrograde Langendorff perfusion model. Sertraline elicited dose-dependent relaxation, independent of the substance used for precontraction (p < 0.025). Sertraline showed a rightward shift of dose-response curves to PE (p < 0.01). Vasodilatory effects of SSRIs were endothelium independent. In perfused rat hearts, sertraline (0.3 to 10 micromol x L(-1)), showed a concentration-dependent increase in coronary flow that returned to baseline levels after wash-out of the antidepressant (p = 0.005). One of the SSRIs, sertraline, showed marked vasodilatory effects in rat aorta and human IMAs. Sertraline elicited vasodilatation in coronary arteries during perfusion of rat hearts. These hemodynamic effects may explain
... Discussion We compared the vasoprotective effect of the ACE-I, lisinopril, vs. ... as area un... more ... Discussion We compared the vasoprotective effect of the ACE-I, lisinopril, vs. ... as area under the curve (AUC), in isolated aortic rings from untreated rats with no myocardial infarction (no-MI), untreated rats with MI (MI) and MI-rats treated with lisinopril (LIS) or candesartan (CAN). ...
Physiological reports, 2015
Women with renal disease progress at a slower rate to end stage renal disease than men. As angiot... more Women with renal disease progress at a slower rate to end stage renal disease than men. As angiotensin II has both hemodynamic and direct renal effects, we hypothesized that the female protection may result from gender differences in responses to angiotensin II. Therefore, we studied gender differences in response to angiotensin II, during acute (human) and chronic (rats) angiotensin II administration. In young healthy men (n = 18) and women (n = 18) we studied the responses of renal hemodynamics ((125)I-iothalamate and (131)I-Hippuran) and blood pressure to graded angiotensin II infusion (0.3, 1.0, and 3.0 ng/kg/min for 1 h). Men had increased responses of diastolic blood pressure (P = 0.01), mean arterial pressure (P = 0.05), and a more pronounced decrease in effective renal plasma flow (P = 0.009) than women. We measured the changes in proteinuria and blood pressure in response to chronic administration (200 ng/kg/min for 3 weeks) of angiotensin II in rats. Male rats had an incre...
European Journal of Heart Failure Supplements
PLoS ONE
Cardiopulmonary bypass (CPB) may induce systemic inflammation and vascular dysfunction. Sphingosi... more Cardiopulmonary bypass (CPB) may induce systemic inflammation and vascular dysfunction. Sphingosine 1-phosphate (S1P) modulates various vascular and immune responses. Here we explored whether agonists of the S1P receptors, FTY720 and SEW2871 improve vascular reactivity after CPB in the rat. Experiments were done in male Wistar rats (total n = 127). Anesthesia was induced by isoflurane (2.5-3%) and maintained by fentanyl and midazolam during CPB. After catheterization of the left femoral artery, carotid artery and the right atrium, normothermic extracorporeal circulation was instituted for 60 minutes. In the first part of the study animals were euthanized after either 1 hour, 1 day, 2 or 5 days of the recovery period. In second part of the study animals were euthanized after 1 day of postoperative period. We evaluated the contractile response to phenylephrine (mesenteric arteries) or to serotonin (coronary artery) and vasodilatory response to acethylcholine (both arteries). Contracti...
Hydrometallurgy
25-75 percentile): 76.5 (70.3-82.9) % and 59.0 (51.7-64.4) %, respectively). Furthermore, CD4 + h... more 25-75 percentile): 76.5 (70.3-82.9) % and 59.0 (51.7-64.4) %, respectively). Furthermore, CD4 + helper and CD8 + cytotoxic T cells showed a similar pattern of intracellular galectin-1 expression in normal pregnancy. However, the proportion of galectin-1-expressing peripheral blood T (both helper and cytotoxic) and NK cells was markedly decreased in preeclampsia (for T cells: 30.6 (21.3-34.4) %, p<0.001; for NK cells: 42.9 (32.0-61.9) %, p<0.001). Conclusions: The majority of circulating NK and -to a lesser extent -T (helper and cytotoxic) cells shows intracellular galectin-1 expression in normal pregnancy. In preeclampsia, the proportion of galectin-1-positive T (both helper and cytotoxic) and NK cells in the peripheral blood is markedly decreased, which might contribute to the development of the generalized intravascular inflammatory reaction characteristic of the maternal syndrome of the disease.
Objective Since the cerebrovasculature likely plays a prominent role in the pathophysiology of ec... more Objective Since the cerebrovasculature likely plays a prominent role in the pathophysiology of eclampsia, we assessed the effects of low-dose endotoxin-induced experimental preeclampsia on the function and structure of rat posterior cerebral arteries (PCA) and mesenteric arteries (MA).Methods Nonpregnant (NP) and pregnant (P) rats were infused with saline (NP-CTL, n = 9; P-CTL, n = 9) or low-dose endotoxin (NP-endotoxin, n = 9; P-endotoxin, n = 10). Myogenic activity, pressure of forced dilatation (FD) and structural properties were evaluated in PCA and MA.ResultsPCA underwent FD between 125 and 150 mmHg in P-endotoxin (repeated measures ANOVA vs 75 mmHg; P < 0.05) and between 150 and 175 mmHg in P-CTL and NP animals (repeated measures ANOVA vs 75 mmHg; P < 0.05). PCA myogenic tone was unaffected by pregnancy or endotoxin, however, pregnancy decreased the MA myogenic tone (P < 0.05 vs NP). Passive characteristics of PCA and MA were unaffected by pregnancy or endotoxin.Concl...
Developments in Cardiovascular Medicine, 1998
Publication of this thesis by financial funds of the following companies is highly appreciated: B... more Publication of this thesis by financial funds of the following companies is highly appreciated: Biotronik, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Menarini, Novartis, Pfizer and Servier Nederland BV.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2013
Objective: Since the cerebrovasculature likely plays a prominent role in the pathophysiology of e... more Objective: Since the cerebrovasculature likely plays a prominent role in the pathophysiology of eclampsia, we assessed the effects of low-dose endotoxin-induced experimental preeclampsia on the function and structure of rat posterior cerebral arteries (PCA) and mesenteric arteries (MA). Methods: Nonpregnant (NP) and pregnant (P) rats were infused with saline (NP-CTL, n = 9; P-CTL, n = 9) or low-dose endotoxin (NP-endotoxin, n = 9; P-endotoxin, n = 10). Myogenic activity, pressure of forced dilatation (FD) and structural properties were evaluated in PCA and MA. Results: PCA underwent FD between 125 and 150 mmHg in P-endotoxin (repeated measures ANOVA vs 75 mmHg; P < 0.05) and between 150 and 175 mmHg in P-CTL and NP animals (repeated measures ANOVA vs 75 mmHg; P < 0.05). PCA myogenic tone was unaffected by pregnancy or endotoxin, however, pregnancy decreased the MA myogenic tone (P < 0.05 vs NP). Passive characteristics of PCA and MA were unaffected by pregnancy or endotoxin. Conclusion: Low-dose endotoxin-infusion during pregnancy, but not pregnancy alone, decreased the pressure of FD in PCA. This may predispose to cerebral autoregulatory breakthrough and edema formation during increased blood pressure as seen in eclampsia.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2010
Background: Peroxisome proliferator-activated receptor-γ (PPAR-γ), a nuclear receptor expressed i... more Background: Peroxisome proliferator-activated receptor-γ (PPAR-γ), a nuclear receptor expressed in placental tissue plays a seminal role in pregnancy. We aimed to 1) investigate the effect of PPAR-γ antagonism during uncomplicated pregnancy in rats 2) investigate the role of PPAR-γ activation during complicated pregnancy using the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia (PE). Methods: On gestational day (GD)11, a miniosmotic pump was inserted into the peritoneal cavity of pregnant rats and either vehicle or the PPAR-γ antagonist, T0070907 (1mg/kg/day), administered between GD11-15. In a separate study, either vehicle or the PPAR-γ agonist, rosiglitazone (5mg/kg/day), was administered (GD16-18) to normal pregnant or RUPP (produced via surgical reduction of uteroplacental perfusion on GD14) rats in either the absence or presence of the heme oxyenase 1 (HO-1) inhibitor, SnPP (50μmol/kg/day), via drinking water. Animals were chronically catheterized on GD18 for mean arterial blood pressure (MABP) measurement on GD19. In all groups, vascular function was assessed in response to the vasoconstrictor, U46619 (10 -9 -4×10 -7 M), and the vasodilators bradykinin (BK; 10 -9 -10 -5 M) and sodium nitroprusside (SNP; 10 -9 -10 -5 M). Results: Rats which received T0070907 had significantly elevated MABP (p<0.05) and impaired vasorelaxation in response to BK (p<0.05) compared with controls. T0070907 treated rats had reduced pup number and weight and significantly increased placental weight (p<0.05) compared with controls. RUPP rats were characterized by severe hypertension (P<0.001) and impaired vasorelaxation in response to BK (P<0.001). Treatment with rosiglitazone reversed RUPP induced hypertension (P<0.001) and endothelial dysfunction (P<0.05). These effects were abrogated by co-administration of SnPP with rosiglitazone (P<0.01). Conclusions: PPAR-γ antagonism results in a 'pre-eclamptic' type model characterised by hypertension, endothelial dysfunction and restricted fetal growth. PPAR-γ activation in the RUPP rat reverses hypertension and endothelial dysfunction through a HO-1 dependent pathway. PPAR-γ agonists may provide a potential therapeutic intervention in the treatment of PE
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Papers by Hendrik Buikema