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Reza Tabrizchi

Publications and source records attributed to Reza Tabrizchi.

17 recordsLinked to original sources
PubMed2006

beta-adrenoceptor mediated responses in rat pulmonary artery: putative role of TASK-1 related K channels.

The effect of isoprenaline on tone, cyclic adenosine 3':5' monophosphate (cAMP), and smooth muscle membrane potential (E ( m )) were assessed in rat isolated pulmonary arteries. N(omega)-nitro-L-arginine methyl ester (10.0 microM) or removal of endothelium partially inhibited relaxant responses to isoprenaline, but glibenclamide (10.0 microM) and indomethacin (10.0 microM) did not. While Rp-8-Br-cAMP (30.0 microM), tetraethylammonium (0.3 & 1.0 mM), 4-aminopyridine (100 microM), anandamide (10.0 microM), charybdotoxin (0.1 microM), ouabain (100 microM), and barium chloride (100 microM), incompletely blocked relaxation to isoprenaline, cyclopiazonic acid (1.0 microM), apamin (3.0 microM) and zinc acetate (300 microM) were without effect. Increasing extracellular K(+) ([K(+)](e)) inhibited relaxant responses to isoprenaline, completely abolishing the response at 30 mM [K+](e). Vasorelaxant effects of isoprenaline were significantly attenuated in buffer pH 6.4, and concomitant presence of Rp-8-Br-cAMP (30.0 microM) in pH 6.4 produced significant additive inhibition when compared to pH 6.4 without Rp-8-Br-cAMP. Isoprenaline increased cAMP turnover (1.55+/-0.24 fold; mean +/- SEM), which was inhibited by propranolol (1.0 microM). Resting E ( m ) of smooth muscle cells was -63.0+/-0.50 mV, and isoprenaline (1.0 microM) produced hyperpolarisation (-73.3+/-0.80 mV). While glibenclamide failed to affect isoprenaline-induced hyperpolarisation, ICI 118,551 (1.0 microM), anandamide or buffer pH 6.4 prevented it, and barium chloride and oubain combined caused partial inhibition. Isoprenaline-mediated relaxation seems to arise from several processes, including the generation of nitric oxide, the cAMP-cascade and, more importantly, a hyperpolarisation that is not due to activation of ATP-sensitive K channels but possibly of two-pore domain K channels of the TASK family.

Animals↗
PubMed2006

Influence of tangential stress on mechanical responses to vasoactive agents in human saphenous vein with and without perivascular adipose tissue.

AIM: Improvement in short-term patency of vein grafts harvested with the surrounding tissue and no distention has been noted. The influence of transient tangential stress on mechanical function to vasoactive agents in isolated human saphenous veins stripped or with attached perivascular adipose tissue was assessed. METHODS: Concentration-response curves to noradrenaline, 5-hydroxytryptamine, methylcholine, sodium nitroprusside and nicardipine were constructed for veins exposed to no, low (approximately 120 mmHg) or high (approximately 240 mmHg) tangential stress. RESULTS: Tangential stress did not affect contractile effects of noradrenaline or relaxant effects of methylcholine and sodium nitroprusside. Regression analysis of the concentration-response curve to 5-hydroxytryptamine revealed a significant (P=0.042) increase in sensitivity in saphenous veins without perivascular adipose tissue exposed to no tangential stress, compared with veins with attached adipose tissue. Exposure to high stress significantly (P=0.024) increased the potency of 5-hydroxytryptamine in blood vessels without perivascular adipose tissue, as opposed to veins with adipose tissue. Relaxant responses to nicardipine in veins with perivascular adipose tissue were significantly (P=0.001) affected by exposure to low tangential stress compared with no or high tangential stress. A parallel comparison revealed that intact veins compared with those without perivascular adipose tissue exposed to low stress were significantly (P=0.020) more resistant to the relaxant effects of nicardipine. CONCLUSION: The findings of the present report support the view that tangential stress has an impact on the actions of vasoactive agents, but this influence is variable and factor(s) released from perivascular adipose tissue may have a bearing on the observed effect.

Adipose Tissue↗
PubMed2005

Peroxisome proliferator-activated receptor gamma as a drug target in the pathogenesis of insulin resistance.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. The activation of PPAR-gamma, an isotype of PPARs, can either increase or decrease the transcription of target genes. The genes controlled by this form of PPAR have been shown to encode proteins or peptides that participate in the pathogenesis of insulin resistance. Insulin resistance is defined as a state of reduced responsiveness to normal circulating concentrations of insulin and it often co-exists with central obesity, hypertension, dyslipidemia, and atherosclerosis. There is substantial evidence that links obesity with insulin resistance and type-2 diabetes. The early phase of obesity-related insulin resistance has 2 components: (a) interruption of lipid homeostasis leading to the increased plasma concentration of fatty acids that is normally suppressed by the activation of PPAR-gamma, and (b) activation of factors such as cytokines depressed by PPAR-gamma that cause insulin resistance. Therefore, it is logical to suggest that activation of PPAR-gamma may partially reverse the state of insulin resistance. Evidently, activation of the nuclear receptor, PPAR-gamma, by thiazolidinediones has been reported to ameliorate insulin resistance. Although hepatotoxity and possibility to induce congestive heart failure (CHF) limit the widely use of thiazolodinediones, they are still powerful weapon to fight against insulin resistance and type-2 diabetes if use properly. This article reviews the physiology of PPAR-gamma and insulin-signaling transduction, the pathogenesis of insulin resistance in obesity-related type-2 diabetes, the pharmacological role of PPAR-gamma in insulin resistance, and additional effects of thiazolidinediones.

Animals↗
PubMed2005

Impact of nitric oxide synthase inhibitor and chloride channel antagonist on mesenteric vascular conductance in anesthetized Dahl normotensive and hypertensive rats.

The effects of nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) and chloride channel antagonist niflumic acid on vascular responsiveness to the effect of alpha1-adrenoceptor stimulation in the mesenteric bed of Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats were examined. Dahl salt-resistant and salt-sensitive rats were fed a high-salt diet (4% NaCl) for 7 weeks, and blood pressure, heart rate, and mesenteric blood flow were measured before and after treatment with L-NAME (0.3 mg/kg, IV) and/or niflumic acid (10 mg/kg, IV). Morphometry of the primary mesenteric blood vessel was also assessed. Administration of alpha1-adrenoceptor agonist cirazoline produced a dose-dependent increase in blood pressure, decrease in heart rate, mesenteric blood flow, and mesenteric vascular conductance in SRN and SSH rats. L-NAME significantly increased basal blood pressure and decreased basal mesenteric blood flow and vascular conductance in SRN but not in SSH rats. Niflumic acid attenuation of cirazoline-mediated decreases in mesenteric blood flow and vascular conductance was more pronounced in the SRN than SSH rats. This difference in the inhibitory actions of niflumic acid was absent following its concomitant administration with L-NAME. It seems that tonic release of nitric oxide modulates niflumic acid-sensitive chloride channels in vascular muscle. Blood vessels from SSH rats had significantly larger smooth muscle thickness and lumen diameter, but the ratio of the 2 were not different between the SRN and SSH. Our findings support the view that alterations in receptor-mediated signal transduction, rather than just changes in blood vessel architecture, are responsible for differences in behavior of blood vessels in salt-induced hypertensive rats.

Animals↗
PubMed2005

Effects of chloride substitution in isolated mesenteric blood vessels from Dahl normotensive and hypertensive rats.

The purpose of this investigation was to examine the effect of Cl-free medium, nitric oxide synthase inhibitor (N nitro-L-arginine methyl ester; L-NAME), and Cl channel antagonist (niflumic acid), on alpha1-adrenoceptor (cirazoline) mediated responses in the isolated mesenteric blood vessels from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet for 7 weeks. Cirazoline produced dose-dependent vasoconstriction in blood vessels of SRN and SSH rats. Replacement of extracellular Cl with propionate ions significantly inhibited (P < 0.05) cirazoline-mediated vasoconstriction in SRN but not in SSH rats. Perfusion with L-NAME (10 microM) augmented responses to cirazoline in SRN but not in SSH rats. In Cl-free medium, addition of L-NAME had a biphasic effect on cirazoline responses; potentiation of responses at the lower doses and attenuation at the highest dose. Niflumic acid (10 microM) significantly inhibited cirazoline responses with the inhibition being more pronounced in SRN than SSH rats. The resting Em of smooth muscle cells was -68.0 +/- 4.2 mV (mean +/- SD; n = 87) and -67.2 +/- 4.8 mV (n = 88), in SRN and SSH rats, respectively. Perfusion with Cl-free medium produced a significant depolarization that was larger in smooth muscle cells of SSH (-57.4 +/- 4.8 mV, n = 38) than SRN (-61.3 +/- 5.4 mV, n = 35) rats, while L-NAME depolarized the smooth muscle cells of SRN (-62.1 +/- 6.5 mV, n = 36) but not SSH (-67.5 +/- 4.2 mV, n = 34) rats. The data supports the view that Cl handling and Ca-dependent Cl channels seem to undergo modification as a consequence of salt-induced hypertension. It is also possible that the modified role of nitric oxide on membrane potential may have a direct bearing on the changes observed in Cl handling in blood vessels of SRN versus SSH rats.

Animals↗
PubMed2004

A comparison between haemodynamic effects of vasopressin analogues.

Some analogues of arginine vasopressin (AVP) reportedly possess hypotensive properties, and two such peptides are Cys(1)-Tyr(2)-Phe(3)-Val(4)-Asn(5)-Cys(6)-Pro(7)- d-Arg(8)-Gly(9)-NH(2) (VD-AVP) and d(CH(2))(5)-Cys(1)- d-Tyr(Et)(2)-Arg(3)-Val(4)-Asn(5)-Cys(6)-Lys(7)-Lys(8)-ethylenediamine(9) (TA-LVP). In the present investigation we examined the effects of TA-LVP (0.3, 1.0 and 3.0 microg/kg/min), VD-AVP (0.3, 1.0 and 3.0 microg/kg/min) and AVP (1.0, 3.0, 10 ng/kg/min) on haemodynamics, blood volume (BV) and plasma troponin levels in anaesthetised rats. Infusion of TA-LVP significantly ( P<0.05) reduced blood pressure (-45+/-3%; n=8; mean +/- SEM), mean circulatory filling pressure ( P(mcf); -41+/-3%), and cardiac output (CO; -59+/-4%). The reduction in CO at a lower dose of TA-LVP was due to reduced venous tone, while at higher doses the reduction was predominantly the result of reduced BV (-35+/-4%). The large decrease in BV during the infusion of TA-LVP, substantially increased resistance to venous return (50+/-11%), which was the main contributor in reducing CO. Administration of AVP significantly increased blood pressure (41+/-4%) and arterial resistance (98+/-16%) without any impact on P(mcf) and BV, while significantly reducing CO (-26+/-5%). Infusion of VD-AVP did not produce hypotension, but produced a modest but significant reduction in CO (-18+/-5%) and insignificant but moderate increases in peripheral resistance (30+/-12%) and resistance to venous return (28+/-8%). Plasma troponin levels were not affected by any of the peptides. The hypotensive action of TA-LVP was due to a reduction in CO as a result of a reduced pre-load, while the pressor effect of AVP increased after-load sufficiently to impede flow, reducing CO. VD-AVP was devoid of any hypotensive effects, suggesting that V(2)-vasopressin receptors are most likely to play a limited role in the control of cardiac and vascular function in these animals.

Animals↗
PubMed2004

Effects of chloride substitution on electromechanical responses in the pulmonary artery of Dahl normotensive and hypertensive rats.

1. We have investigated the in vitro interaction between chloride ions and endothelium as revealed by alterations in vascular contractility and smooth muscle cell membrane potential in isolated pulmonary arteries from Dahl salt-resistant normotensive and salt-sensitive hypertensive rats. 2. Exposure to nitro-l-arginine methyl ester (l-NAME) of tissues from normotensive but not hypertensive rats augmented contractions to cirazoline. While chloride removal did not alter cirazoline-induced contractions, it completely abolished the augmentation by l-NAME in normotensive rats. However, in hypertensive rats, removal of chloride ions significantly attenuated contractions elicited by cirazoline, and l-NAME effectively reversed this inhibition. 3. Methacholine-induced endothelium-dependent relaxations of the same magnitude were evident in both normotensive and hypertensive rats. However, basal cyclic GMP levels were found to be significantly higher (7.8-fold) in blood vessels of normotensive rats compared to hypertensive rats. 4. The resting membrane potential in pulmonary arteries of hypertensive rats (-52.1+/-1.04 mV) revealed a significant hyperpolarisation when compared with that of normotensive rats (-46.4+/-1.58 mV). Cirazoline did not produce a significant depolarisation in blood vessels of either normotensive or hypertensive rats. Perfusion with chloride-free solution resulted in a modest but significant hyperpolarisation (-8.0 mV) in the blood vessels of hypertensive but not in normotensive rats. 5. We conclude that salt-dependent hypertension in Dahl rats is accompanied by functional and biochemical changes in low-pressure blood vessels. These changes can, in part, be attributed to impairment in the basal, but not methacholine-stimulated, release of nitric oxide, and to altered chloride ion handling.

Adrenergic alpha-Agonists↗
PubMed2004

Hyperhomocysteinemia and the risk of restenosis after coronary artery stenting: fact or fiction?

The incidence of restenosis after coronary artery stent placement is approximately 38%. An interesting view has been stipulated: that hyperhomocysteinemia may be partly responsible for in-stent restenosis. Epidemiologic evidence exists that is persuasive in suggesting that individuals with occlusive vascular disease have a higher blood homocysteine concentration than control subjects. Thus, elevated plasma levels of homocysteine have been implicated as a risk factor for coronary artery disease. The composition of the current clinical knowledge on the question of whether hyperhomocysteinemia is a significant factor for restenosis of coronary artery stents consists of several trials with different approaches, objectives and outcomes. However, the current studies that have been published in the peer-reviewed medical literature have not reached a consensus as to whether an elevated plasma level of homocysteine is an independent risk factor responsible for restenosis following stent implantation. Our current knowledge as to the place of plasma homocysteine levels in the development of in-stent restenosis seems incomplete, and in the realm of homocysteine and restenosis of stents, there are plenty of questions that still remain to be answered.

Age Distribution↗
PubMed2003

Haemodynamic effects of endothelin receptor antagonist, tezosentan, in tumour necrosis factor-alpha treated anaesthetized rats.

Administration of tumour necrosis factor-alpha (TNF-alpha) produces progressive reduction in cardiac output (CO) by affecting preload, afterload and cardiac contractility. We have examined the effect of an endothelin receptor antagonist, tezosentan (1, 3 or 10 mg/kg), on CO, heart rate (HR), blood pressure (BP), mean circulatory filling pressure (P(mcf)), resistance to venous return (RVR), arterial resistance (AR), dP/dt, stroke volume (SV), plasma levels of NO(2)(-)/NO(3)(-), and inducible nitric oxide synthase (iNOS) activity in lungs, ex vivo, following treatment with TNF-alpha (30 microg/kg) in anaesthetized rats. Treatment with TNF-alpha alone resulted in significant reduction in CO (40+/-4%), dP/dt (24+/-2%), P(mcf) (24+/-2%), BP (21+/-3%) and SV (38+/-5%) ( n=6; mean +/- SEM), and significant increases in RVR (38+/-9%) and AR (45+/-6%). There were no significant changes in HR or in plasma levels of NO(2)(-)/NO(3)(-) in animals treated with TNF-alpha but there was a modest but significant increase in iNOS activity. Tezosentan alone did not have any effect on haemodynamics, plasma levels of NO(2)(-)/NO(3)(-) or iNOS activity. Tezosentan at the highest dose abolished the effects of TNF-alpha on dP/dt, AR, and RVR. In animals treated with a combination of TNF-alpha and highest dose of tezosentan CO, P(mcf), BP, and SV were reduced by 28+/-5%, 16+/-3%, 21+/-4%, and 27+/-5%, respectively. Tezosentan was able to inhibit the negative impact of TNF-alpha on AR and dP/dt but not on P(mcf). It is likely that the negative impact of TNF-alpha on CO in tezosentan-treated animals could be entirely attributed to reduction in preload.

Animals↗
PubMed2003

The influence of calcium channel antagonists on isolated human distal radial arteries.

A comparison was made between the efficacies and potencies of calcium channel antagonists on contractions induced by 5-hydroxytryptamine, norepinephrine, or high-potassium buffer in isolated human distal radial arteries. Also, the impact of removal of extracellular calcium ions on contractions induced by 5-hydroxytryptamine or norepinephrine was assessed. Isometric contractions were induced by agonists, and relaxant responses to calcium channel antagonists, nifedipine, diltiazem, verapamil, or mibefradil were examined. 5-hydroxytryptamine-induced contractions when compared with norepinephrine or high-potassium induced contractions were significantly more sensitive to inhibition by nifedipine (pIC50 = 7.53 +/- 0.15; 6.78 +/- 0.12; 6.6 +/- 0.22, respectively, mean +/- SEM). Diltiazem was more effective in producing relaxations when contractions were elicited with 5-hydroxytryptamine (pIC50 = 6.48 +/- 0.84) or norepinephrine (pIC50 = 6.20 +/- 0.21) than with high potassium (pIC50 = 5.43 +/- 0.10). Verapamil was more effective at relaxing arteries contracted with 5-hydroxytryptamine (pIC50 = 6.09 +/- 0.19) or norepinephrine (pIC50 = 6.00 +/- 0.17) than with high potassium (pIC50 = 5.60 +/- 0.16). Mibefradil was not very effective in producing relaxations. The studies revealed that removal of extracellular calcium significantly attenuated contractions produced by 5-hydroxytryptamine (-67.7 +/- 6.3%) and norepinephrine (-89 +/- 1.5%). In conclusion, our data indicates that nifedipine was the most effective drug in producing relaxations; also, contractions produced by 5-hydroxytryptamine and norepinephrine were found to be critically dependent on the presence of extracellular calcium.

Adult↗
PubMed2003

Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders.

Elevated blood pressure is a risk factor for a variety of cardiovascular disorders, including coronary heart disease, peripheral vascular disease, cardiac failure and cerebrovascular disease. The prevailing view is that an elevated systolic rather than diastolic blood pressure is the major contributor in mortality and morbidity attributed to cardiovascular disorders. Isolated high systolic blood pressure, especially in the elderly, is a major risk factor and should undoubtedly be a target for drug treatment. In the general population, systolic and diastolic blood pressure are highly correlated, and thus it is difficult to dissociate the effects of these two components of the blood pressure and specifically ascribe cardiovascular risk factors to just elevated systolic blood pressure. Therefore, the goal in therapy of an individual with hypertension must be to reduce elevated systolic and diastolic blood pressure in order to reduce mortality and morbidity. ACE and neutral peptidase inhibitors are a new class of drugs that may be beneficial in the treatment of patients with hypertension and heart failure. They may also be useful in the treatment of diabetic patients with hypertension and/or heart failure. Drugs of this class are dual inhibitors of ACE and neutral endopeptidase, and are capable of affecting vascular tone and fluid balance. They are capable of producing vasodilatation by virtue of inhibiting the production of angiotensin II, degradation of natriuretic peptides and bradykinin. They also appear to promote natriuresis and diuresis by amplifying the actions of natriuretic peptidase and reducing aldosterone effects. In addition, they should also attenuate trophogenic actions of the renin angiotensin system and the sympathetic nervous system. Omapatrilat is one drug that appears to be at the advanced stages of clinical development. This drug has been shown to be quite effective in the treatment of hypertension. Evidence also seems to indicate that treatment with omapatrilat results in a higher tendency towards preventing death and worsening heart failure when compared with treatment with a pure ACE inhibitor in patients with advanced heart failure. Overall safety with omapatrilat appears to be good, but like other ACE inhibitors the incidence of cough is higher when compared with placebo. Other common adverse effects noted are headaches, facial flushing/warm sensation, dizziness, nausea and dyspnoea. Of greater concern is the occurrence of angio-oedema, the true incidence of which remains to be fully established as part of the published medical literature.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

SLV-306. Solvay.

SLV-306 is an orally active mixed neutral endopeptidase/endothelin converting enzyme inhibitor under development by Solvay SA for the potential treatment of essential hypertension and congestive heart failure. The compound is currently undergoing phase II clinical trials in Belgium.

Animals↗
PubMed2002

A comparative study of the effects of Cl(-) channel blockers on mesenteric vascular conductance in anaesthetized rat.

There is evidence to suggest that niflumic acid is capable of selectively inhibiting Ca(2+)-dependent Cl(-) channels. Furthermore, it has been demonstrated that niflumic acid is capable of antagonizing contractile responses due to activation of alpha(1)-adrenoceptor in mesenteric vasculature. Here, we have examined the effects of three Cl(-) channel blockers, niflumic acid, indanyloxyacetic acid 94 (IAA-94) and diphenylamine-2-carboxylic acid (DPC) on cirazoline-mediated vasoconstriction in mesenteric blood vessel in vivo. Infusion of cirazoline produced a dose-dependent increase in blood pressure, decrease in superior mesenteric blood flow, mesenteric vascular conductance and heart rate. While niflumic acid and IAA-94 did not have any impact on cirazoline-induced changes in blood pressure, DPC accentuated the pressor effect of cirazoline. Neither agent affected cirazoline-mediated reflex reduction in the heart rate. Niflumic acid, IAA-94 and DPC attenuated alpha(1)-adrenoceptor mediated decrease in mesenteric blood flow and vascular conductance. Based on the profile of the actions of these compounds, it may be suggested that IAA-94 did not appear to act as selective inhibitor of Ca(2+)-activated Cl(-) channels when compared to niflumic acid in the mesenteric blood vessels. In addition, while DPC seems to be as effective as niflumic acid in its effects on mesenteric blood vessels, its actions may be attributed to other pharmacological effects.

Animals↗
PubMed2002

Comparative study of functional responses and morphometric state of distal radial arteries in male and female.

BACKGROUND: Differences can exist in terms of physiology and morphology of blood vessels on the basis of gender. Radial artery is now considered to be the second choice for coronary artery bypass grafting. However, there is a lack of comparative studies on the function and morphometery of radial arteries in female and male patients. METHODS: Radial arteries from 9 female and 9 male patients undergoing coronary artery bypass grafting were used to compare the effects of vasoconstrictors, noradrenaline and 5-hydroxytryptamine, as well as the influence of endothelium-dependent (with methacholine) and endothelium-independent (with sodium nitroprusside) relaxations. Furthermore, morphomteric measurements of smooth muscle thickness, lumen perimeter, lumen area, and intima area (including plaque) of distal radial arteries from female and male patients were also made. RESULTS: Radial arteries from female patients when compared to male patients were significantly more sensitive to the actions of noradrenaline, and somewhat more sensitive towards the actions of 5-hydroxytryptamine. However, no significant differences were found between the relaxant effects of methacholine in radial arteries of female and male patients. In contrast, radial arteries from female patients when compared to male patients were significantly less sensitive to the relaxant effects of sodium nitroprusside. Morphometric measurements of blood vessels from female and male patients revealed that vessels obtained from female patients had a smaller lumen area and perimeter than vessels from male patients. In contrast, there were no significant differences between tunica intima area (including plaque area) or smooth muscle thickness in radial arteries of female patients when compared to male patients. However, the radial arteries from female patients had a significantly greater ratio of tunica intima area (including plaque) to lumen area when compared with radial arteries from male patients. CONCLUSIONS: Differences exist between the functional behavior and morphometery of radial arteries of female and male patients. It is possible that postbypass, radial artery graft may show different characteristics in female versus male patients.

Aged↗
PubMed2002

Effect of nitric oxide synthase inhibitor N(omega) nitro-L-arginine methyl ester on relaxant responses to calcium channel antagonists in isolated aortic rings from Dahl normotensive and hypertensive rats.

Differences exist between the pharmacological actions of calcium channel antagonists in blood vessels from hypertensive versus normotensive animals. In this investigation, we have examined the impact of nitric oxide synthase inhibitor N(omega) nitro-L-arginine methyl ester (L-NAME) on relaxant responses produced by the calcium channel antagonists (nifedipine, diltiazem, and mibefradil) in isolated aortic rings from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet. Morphological examination of the aortic rings revealed significantly larger lumen area, smooth muscle wall thickness, and perimeter in vessels of SSH rats versus SRN rats. Rank order potency for the antagonists was nifedipine > mibefradil > or = diltiazem in aortic rings from SRN rats, but mibefradil was found to be the most efficacious. The rank order potency for the antagonists in aortic rings from SSH rats was nifedipine > diltiazem > mibefradil, although all three drugs showed similar efficacy. The presence of L-NAME attenuated relaxations elicited by the antagonists in aortic rings from SRN rats. Treatment of tissues with L-NAME significantly reduced maximal response and decreased pIC(50). The presence of L-NAME had no effects on concentration-response curves to nifedipine and diltiazem in aortic rings from SSH rats, but it significantly attenuated relaxant responses of mibefradil. Our current results support the view that these calcium channel antagonists produce relaxations by mechanisms that are sensitive and insensitive to L-NAME. Moreover, the component insensitive to L-NAME was lacking in tissues from SSH rats for nifedipine and diltiazem but not mibefradil.

Animals↗