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 established. We investigated the responses to phenylephrine and acetylcholine in rat mesenteric resistance artery and aorta mounted in vitro in myographs after a 2-week treatment with endothelin-1 (5 pmol kg(-1) min(-1), n = 8). Systolic arterial blood pressure increased in endothelin-1-treated rats (171 +/- 7 mmHg vs. 196 +/- 6 mmHg, P < 0.05). In the aorta, chronic endothelin-1 significantly increased the dilator response 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 NG-nitro-L-arginine methyl ester (L-NAME 100 micromol/l) and partly restored by cyclooxygenases inhibition (indomethacin, 10 micromol/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 constrictor cyclooxygenase product(s). In mesenteric resistance arteries chronic endothelin-1 increased the participation of cyclooxygenase products in acetylcholine-induced dilatation from 10 +/- 2 to 19 +/- 3%. In both types of arteries, phenylephrine-induced contraction was not affected by chronic endothelin-1. Thus chronic endothelin-1 increased the participation of dilator cyclooxygenase product(s) in acetylcholine-induced dilatation in the aorta and the mesenteric resistance arteries.
Iglarz
M
M
Institut National de la Santé et de la Recherche Médicale U 141, IFR Circulation-Lariboisière, Université Paris VII, Hôpital Lariboisière, France.
Lévy
B I
BI
Henrion
D
D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D000109:Acetylcholine