CHRONIC ENDOTHELIN-1-INDUCED CHANGES IN VASCULAR REACTIVITY IN RAT RESISTANCE ARTERIES AND AORTA

The role of endothelin-1 in vascular homeostasis is not yet clearly es tablished. We investigated the responses to phenylephrine and acetylch oline in rat mesenteric resistance artery and aorta mounted in vitro i n myographs after a 2-week treatment with endothelin-1 (5 pmol kg(-1) min(-1), n = 8). Systolic arterial blood pressure increased in endothe lin-l-treated rats (171 +/- 7 mmHg vs. 196 +/- 6 mmHg, P < 0.05). In t he aorta, chronic endothelin-1 significantly increased the dilator res ponse to acetylcholine (maximal dilatation: 76 +/- 3 vs. 86 +/- 3% in control, P < 0.05). Acetylcholine-induced dilatation was decreased by nitric oxide (NO) synthase inhibition with N-G-nitro-L-arginine methyl ester (L-NAME 100 mu mol/l) and partly restored by cyclooxygenases in hibition (indomethacin, 10 mu mol/l). In endothelin-1-treated rats, L- NAME-sensitive acetylcholine dilatation was lower than in the control, but dilator cyclooxygenase product(s) were found instead of constrict or cyclooxygenase product(s). In mesenteric resistance arteries chroni c endothelin-l increased the participation of cyclooxygenase products in acetylcholine-induced dilatation from 10 +/- 2 to 19 +/- 3%. In bot h types of arteries, phenylephrine-induced contraction was not affecte d by chronic endothelin-1. Thus chronic endothelin-1 increased the par ticipation of dilator cyclooxygenase product(s) in acetylcholine-induc ed dilatation in the aorta and the mesenteric resistance arteries. (C) 1998 Elsevier Science B.V. All rights reserved.