Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats

In the present study we analyzed mesenteric vascular reactivity of chronic nitric oxide (NO)-deficient hypertensive rats (N-W-nitro-L-Arginine Methyl Ester, L-NAME, 50 mg/kg/day, oral, 3 weeks). Perfusion pressure changes in response to cumulative additions of methoxamine and KCI were significantly increased in the mesenteric vessels of the L-NAME-treated as compared with vessels of the controls. Verapamil reduced the responses to methoxamine, bu t those of the hypertensive rats were still enhanced. In contrast, response s to KCl were almost completely abolished by verapamil. In mesenteric vesse ls perfused with zero calcium and high-potassium Krebs, presser responses t o the re-addition of calcium were also significantly enhanced in the hypert ensive rats compared to the controls. Vasodilator responses to acetylcholin e in KCl-preconstricted vessels, while still significant, were reduced in t he L-NAME-treated rats. In this case, acute inhibition of NO blocked the va sodilator responses to acetylcholine and abolished the differences between the two groups. In methoxamine-preconstricted vessels and in the presence o f acute inhibition of NO and prostaglandins, vasodilator responses to acety lcholine were significantly greater in the hypertensive vessels than in con trols. In conclusion, the mesenteric vessels of L-NAME hypertensive rats sh ow an enhanced response to vasopressors which is related to calcium entry. These data also reveal the existence of an enhanced role of a NO and prosta glandin-independent vasodilator factor, probably endothelium-derived hyperp olarizing factor that may play a compensatory role in the deficiency of NO. (C) 2001 Elsevier Science B.V. All rights reserved.