Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet

Abstract

Cordaillat M, Fort A, Virsolvy A, Elghozi J-L, Richard S, Jover B. Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet. Am J Physiol Regul Integr Comp Physiol 292: R1557-R1562, 2007. First published December 21, 2006; doi:10.1152/ajpregu.00624.2006.-Vascular smooth muscle cell contraction and endothelium-dependent relaxation was evaluated in aortic rings isolated from weaned, 5-moold Sprague-Dawley rats fed a normal (NS; 0.8% NaCl) or high (HS; 8% NaCl) sodium diet. Arterial pressure was 140 Ϯ 6 (NS) and 145 Ϯ 6 mmHg (HS). In endothelium-denuded rings, the response to phenylephrine (PE) was not modified by the sodium diet, while that of depolarizing agent KCl and intracellular calcium releasing agent caffeine increased in the HS group. When endothelium was preserved, PE-evoked contraction was reduced in both NS and HS groups, the contraction being yet lower in the HS group. This effect was partially obliterated by addition of N G -nitro-L-arginine methyl ester (L-NAME), independently of the sodium diet. Relaxation to ACh in intact rings and to sodium nitroprusside (SNP) and 8-bromoadenosine 3Ј5Ј cyclic guanosine monophosphate (8-BrcGMP) in the absence of endothelium was enhanced in rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was shifted to the right in the presence of iberiotoxin, an inhibitor of large conductance, voltagedependent, and calcium-sensitive potassium channel (BKCa). However, shift was more marked in rings from HS rats. Present results provide evidence that response of vascular smooth muscle cell to nitric oxide/cGMP-related compounds is increased in HS rings and is associated with a greater activation of the repolarizing BKCa channels. Such changes might counterbalance enhanced contractile response to membrane depolarization and thus participate in maintenance of arterial pressure in the present model of early and long-term HS feeding in rats. vascular smooth muscle cell; endothelial cell; sodium nitroprusside; iberiotoxin.EXCESSIVE CONSUMPTION OF SODIUM is reported to induce cardiac, vascular, and renal alterations in normotensive and hypertensive humans and animals (9, 30). In various strains of rat, a high salt (HS) diet is associated with changes in the reactivity of aortic rings. Many studies conducted in salt-loaded models have shown an increased contraction of vascular smooth muscle cells in response to agonists (1,14). In addition, relaxation evoked by acetylcholine (ACh) or sodium nitroprusside (SNP) was obliterated in aortic rings isolated from adult spontaneously hypertensive and Dalh-sensitive rats fed a 8% NaCl diet for 4 -8 wk (12,14,16). These results suggest that concomitant increase in vascular smooth muscle cell contraction and impaired endothelium-dependent relaxation both participate in the development of hypertension in the salt-sensitive strains. In contrast, an enhanced influence of nitric oxide (NO) may have a major role in the lack of rise in blood pressure of sodiumr...

Time‐course Reduction of Renal Function in Rats on High Sodium Intake: Acute Reversal by Potassium Canrenoate

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