Endothelin-1 produces heterogeneous regional haemodynamic effects in conscious rabbits

P. Roberts-Thomson, R. J. McRitchie, J. P. Chalmers

Research output: Contribution to journalArticle

2 Citations (Scopus)

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-1. The effects of the following antagonists on these reponses were examined: phentolamine, propranolol, 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 ± 73% (n = 12). Mesenteric resistance increased by 420 ± 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 vasodilatation, and that endothelin-1-induced vasoconstriction is attenuated by release of NO.

Original languageEnglish
Pages (from-to)145-169
Number of pages25
JournalClinical and Experimental Hypertension
Volume18
Issue number2
DOIs
Publication statusPublished - 1996
Externally publishedYes

Keywords

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

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