Fm. Ruiz-marcos et al., Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats, EUR J PHARM, 412(3), 2001, pp. 273-279
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.