Impaired potentiation by endothelin-1 and vasopressin of sympathetic contraction in tail artery from hypertensive rats

Objective: To analyse the effects of endothelin-l and vasopressin on the sympathetic vasoconstriction during hypertension. Methods: Electrical field stimulation (4 Hz) was applied to isolated, 2 mm segments: of the tail artery from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats prepared for isometric tension recording. Results: The contraction to electrical stimulation was potentiated by endothelin-1 (10(-10)-10(-8) M) in arteries from WKY but not: from SHR, and by vasopressin (10(-12)-10(-10) M) more markedly in arteries from WKY than from SHR. The potentiation by endothelin-l was reduced more markedly by the antagonist of endothelin ET, receptors BQ-123 (10(-5) M) than by the endothelin ET, receptor antagonist BQ-788 (10(-5) M). The potentiation by vasopressin was reduced by the antagonist of vasopressin V-1 receptors d(CH2)(5)Tyr(Me)AvP (10(-7) M), but not by the vasopressin V-2 receptor antagonist d(CH2)(5)D-Ile(2), Ile(4)AVP (10(-7) M). The blocker of L-type calcium channels verapamil (10(-5) Evf) reduced the potentiation by both endothelin-l and vasopressin in arteries from WKY rats, and increased the potentiation by vasopressin in arteries from SHR. Noradrenaline (10(-8)-10(-4) M) contraction was not modified by endothelin-l (3x10(-9) M) or vasopressin (3x10(-11) M), and contraction to endothelin-l (10(-9)-10(-7) M) and vasopressin (10(-10)-10(-7) M) was lower in arteries from SHR than from WKY rats. Conclusions: (1) the potentiation by endothelin-l and vasopressin of the sympathetic vasoconstriction, probably due to increased release of noradrenaline, is impaired during hypertension, and (2) this potentiation is mediated mainly by endothelin ET, receptors, and by vasopressin VI receptors, in both WKY and SHR, and for both peptides it is mediated by L-type calcium channels in arteries from normotensive but not in those from hypertensive animals. (C) 2000 Elsevier Science B.V. All rights reserved.