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.

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.

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.

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.