Role of nitric oxide in vascular hyper-responsiveness to norepinephrine in hypertensive Dahl rats

Objective To determine whether the abnormal vascular responses observed in salt-sensitive hypertension are caused by an impairment in vascular nitric oxide function. Design Isometric tension was measured in aortic rings isolated from Dahl salt-sensitive and salt-resistant rats fed a regular-salt (0.4% NaCl) or a high-salt (8% NaCl) diet, with and without inhibition of endogenous nitric oxide synthesis. Methods and results Systolic arterial pressure, measured weekly by the tail-cuff method, increased markedly in DS rats with a high-salt diet but did not increase in the other groups, In aortic rings, norepinephrine evoked dose-dependent contractions which were significantly increased in rings from DS rats with a high-salt diet, Pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased the norepinephrine-induced contraction in all groups and abolished differences in contractile responses between high-salt DS rats and the other groups. Acetylcholine induced endothelium-dependent relaxation, which was significantly depressed in high-salt DS rats, L-NAME attenuated the acetylcholine-induced relaxation in all groups and abolished the difference in relaxation response between high-salt DS rats and the other groups. Sodium nitroprusside-induced relaxation was significantly depressed in high-salt DS rats. Conclusions Vascular hypercontractile responses to norepinephrine in DS hypertensive rats can, in part, be explained by an impairment in endothelial nitric oxide production, J Hypertens 1998, 16:1611-1618 (C) Lippincott Williams & Wilkins.