Endothelin-1 Produces Heterogeneous Regional Haemodynamic Effects in Conscious Rabbits

Abstract

Blood flow in the renal artery, superior mesenteric artery and infra-renal abdominal aorta of conscious rabbits was measured by Doppler ultrasound. Arterial pressure, heart rate and blood flow responses were assessed following 0.2 and 0.8 nmol/kg intravenous endothelin-J. The effects of the following antagonists on these responses were examined: phentolamine, propranoloi, scopolamine, captopril, nifedipine, indomethacin, the V₁-vasopressin receptor antagonist d(CH₂)₅Tyr(Me)AVP and the competitive nitric oxide (NO) synthase inhibitor N^G-nitro L-arginine (NOLA). Hindlimb resistance and arterial pressure responded in two phases, initial vasodilatation followed by vasoconstriction. Renal and mesenteric vasoconstriction occurred without initial vasodilatation. Following 0.2 nmol/kg endothelin-1, arterial pressure decreased by 18.5 ± 0.8 mmHg, then increased by 25.2 ± 1.7 mmHg (n = 27). Heart rate changed reciprocally. Renal resistance increased by 533 f 73% (n = 12). Mesenteric resistance increased by 420 f 34%. Hindlimb resistance decreased 54 ± 2% (n = 12, all P < 0.01) then increased slightly (P < 0.05). All changes were greater at 0.8 nmol/kg, particularly the hindlimb vasoconstriction. The only antagonist to alter significantly these responses was NOLA, which in the hindlimb attenuated the vasodilatation and accentuated the vasoconstriction. We conclude that most of the haemodynamic effects of endothelin-1 are direct, but that NO generated by NO synthase causes part of the hindlimb vasodilatati, and that endothelin- 1-induced vasoconstriction is attenuatted by release of NO.

Key Words:

• arterial blood pressure
• conscious rabbit
• endothelin
• haemodynamics
• heart rate
• hindlimb blood flow
• mesenteric blood flow
• renal blood flow