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Effects of the non‐peptide, non‐selective endothelin antagonist, bosentan, on regional haemodynamic responses to N G ‐monomethyl‐L‐arginine in conscious rats
Author(s) -
Gardiner S.M.,
Kemp P.A.,
March J.E.,
Bennett T.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15409.x
Subject(s) - bosentan , omega n methylarginine , endocrinology , endothelin receptor , vasoconstriction , medicine , hemodynamics , vasodilation , nitric oxide , plasma renin activity , blood pressure , renin–angiotensin system , nitric oxide synthase , receptor
1 Male, Long Evans rats (350–450 g) were chronically instrumented to allow monitoring of mean arterial blood pressure, heart rate and changes in renal, mesenteric and hindquarters haemodynamics. In the first experiment, animals ( n = 8) were given a bolus i.v. injection of the nitric oxide synthase inhibitor, N G ‐monomethyl‐L‐arginine hydrochloride (L‐NMMA; 30 mg kg −1 ) on four consecutive days. Fifteen min prior to L‐NMMA administration on the fourth day, the endothelin, ET A ‐, ET B ‐receptor antagonist, bosentan, was injected (30 mg kg −1 , i.v.). Relative to the response on the third day, bosentan caused 33±4%, 24±3%, 14±3%, and 18±5% inhibition of the pressor, and renal, mesenteric and hindquarters vasoconstrictor effects of L‐NMMA, respectively. 2 In the second experiment, bosentan was given 15 min before L‐NMMA in a group of rats ( n = 6) which had not received L‐NMMA previously. Relative to the responses to L‐NMMA on the first day in the previous experiment, bosentan caused a 30%, 24%, 18% and 27% inhibition of the pressor, and renal, mesenteric and hindquarters vasoconstrictor effects of L‐NMMA, respectively. 3 The results indicate a significant contribution from endothelin to the haemodynamic effects of L‐NMMA in conscious rats. However, since our previous studies have shown the renin‐angiotensin and sympathoadrenal systems are not involved, it is likely that the major component of the cardiovascular response to L‐NMMA in conscious rats is due to loss of vasodilator action of endothelial nitric oxide.