Premium
Roles of endothelin receptors in the regional and systemic vascular responses to ET‐1 in the anaesthetized ganglion‐blocked rat: use of selective antagonists
Author(s) -
Allcock Graham H.,
Warner Timothy D.,
Vane John R.
Publication year - 1995
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.1476-5381.1995.tb15099.x
Subject(s) - endocrinology , medicine , endothelin receptor , vasoconstriction , chemistry , receptor , vasodilation , antagonist , receptor antagonist , endothelin 1
1 Endothelin‐1 (ET‐1) produces vasoconstriction, via activation of ET A and ET B receptors on vascular smooth muscle, and vasodilatation via ET B receptors on endothelial cells. Here we have used the ET A receptor‐selective antagonist, BQ‐123, the ET B receptor‐selective antagonist, BQ‐788 and the ET A /ET B receptor non‐selective antagonist, PD 145065, to study the role of these receptors in mediating the haemodynamic changes induced by an infusion of ET‐1 to the anaesthetized ganglion‐blocked rat. 2 Infusion of ET‐1 (10 pmol kg −1 min −1 ) increased the mean arterial pressure (MAP) by 57.5 ± 5.1 mmHg over 70 min. This pressor response was reduced by about 50% by coinfusion of BQ‐123 (10 nmol kg −1 min −1 ), but was unaffected by either BQ‐788 (10 nmol kg −1 min −1 ) or PD 145065 (10 nmol kg −1 min −1 ). 3 After infusion of ET‐1 for 70 min the cardiac output had fallen from 102.6±11.3 to 55.7 ± 7.6 ml min −1 and the total peripheral resistance had increased from 3.24 ± 0.6 to 10.0±0.8 mmHg ml −1 min −1 (per 100g body weight). BQ‐123 decreased the magnitudes of these changes whereas BQ‐788 potentiated them. PD 145065 was without effect. 4 ET‐1 increased the vascular resistances of all the organs studied except the brain and stomach. These changes were attenuated by BQ‐123 in the kidneys, skin, adrenal glands and caecum and potentiated by BQ‐788 in the kidneys, small intestine, large intestine and mesentery. PD 145065 had little effect on the individual tissues. 5 Thus, BQ‐123, a selective ET A receptor antagonist, inhibits the pressor and vascular constrictor effects of ET‐1 more actively than PD 145065. As BQ‐788 potentiates some of the vasoconstrictor effects of ET‐1 and increases the effects of ET‐1 on total peripheral resistance, the predominant role of ET B receptors in the rat circulation is to limit the pressor effects of ET‐1.