Vascular acetylcholine response during chronic NO synthase inhibition: in vivo versus in vitro

Abstract

Objective: The aim of this study was to compare the response to NO-mediated vasodilators in vivo and in vitro during chronic NO synthase inhibition. Methds: NG-Nitro-L-arginine-methyl ester (L-NAME, 0.4 g/l) or vehicle was administered in the drinking water for 6 weeks to male Wistar rats weighing 220-240 g. The effect of acetylcholine and sodium nitroprusside was examined in vivo, on systemic blood pressure and heart rate and in vitro, on the precontracted isolated mesenteric artery. The in vivo response to both vasodilators was examined in awake rats monitored by an indwelling catheter in the femoral artery. Isolated segments of the third-generation mesenteric artery were examined in vitro with a Mulvany dual myograph after precontraction with noradrenaline. Resultsr In isolated mesenteric arteries obtained from rats chronically treated with L-NAME, the initial relaxant response to acetylcholine was significantly decmased whereas that to sodium nitroprusside was enhanced. A late acetylcholine-induced contractile response was present and abolished by indomethacin. In vivo, the hypotensive action of sodium nitroprusside was also enhanced in the L-NAME-treated rats. Acetylcholine reduced blood pressure in the L-NAME-treated hypertensive animals more than in normotensive controls, but less than in control rats infused intravenously with noradrenaline at a dose increasing their blood pressure to hypertensive levels. Conclusions: The NO-mediated vasodilation induced by acetylcholine is attenuated during chronic NO synthase inhibition, both in vivo and in vitro. The blunted hypotensive response to acetylcholine can be demonstrated only if blood pressure of control rats is acutely increased to hypertensive levels.

Selective impairment of endothelium-mediated vasodilation in liver transplant recipients with cyclosporin A -induced hypertension

“…It can be secondary to a pharmacological effect of the drug on the endothelium. In this regard, it has been shown that in vivo inhibition of nitric oxide biosynthesis by chronic administration of L-arginine analogues leads to a reduced response of rat arterioles to norepinephrine, 26 a situation comparable with the one observed in the present study in which CsA caused a severe impairment in nitric oxide mediated vasorelaxation.…”

Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

“…In the present study, the enhanced extent of hypotension in SHR did not change after administration of molsidomine or PETN. The present findings are similar to those obtained in NO-deficient hypertension (6,8) although the etiopathogenic background, NO production, NO level, and cGMP level are different in these two experimental models of hypertension (29).…”

“…Even NO release, measured directly close to the endothelial layer in the femoral artery of the dog, decreased after NO synthase inhibition (4). In contrast, experiments performed on conscious animals, animals under anesthesia, and moreover, under various types of anesthesia, with NO synthase inhibition and consequent increased blood pressure, have demonstrated hypotension elicited by ACh (5)(6)(7). Previous studies by our group showed paradoxically amplified ACh hypotension not only after a short period of time (1-2 h) but also 6 weeks after NO synthase inhibition, which was accompanied by sustained high blood pressure (8).…”

Contractility and Endothelium-Dependent Relaxation of Resistance Vessels in Polycystic Kidney Disease Rats

“…ACh may have other effects on the endothelium, and may cause the release of endothelial-derived contracting factor (EDCF) or endothelial-derived hyperpolarizing factor (EDHF) [22]. In the absence of endothelium, ACh constricts the small resistance vessel [23].…”