Incomplete inhibition of the pressor effects of endothelin‐1 and related peptides in the anaesthetized rat with BQ‐123 provides evidence for more than one vasoconstrictor receptor

Open Access
Publisher Website
Google Scholar
Abstract
1 The effects of the ETA receptor antagonist, BQ-123 on blood pressure changes induced by various members of the endothelin (ET)/sarafotoxin (SX) peptide superfamily were investigated in the anaesthetized rat. 2 ET-1 (1 nmol kg−1, i.v. bolus) induced a sustained increase in mean arterial pressure (MAP, maximum increase 44 ± 3 mmHg). Intravenous injection of BQ-123 at 0.2, 1.0 or 5.0 mg kg−1 5 min before ET-1 inhibited the pressor response by 18, 50 and 61%, respectively. The ET-1 pressor response was inhibited by 75% when the peptide was given 60 min after the start of a 120 min i.v. infusion of BQ-123 (0.2 mg kg−1 min−1). 3 In addition to ET-1, BQ-123 (1 mg kg−1, i.v. bolus) attenuated the pressor responses to big ET-1 (1 nmol kg−1, i.v., bolus, maximum increase in MAP: 68 ± 7 mmHg), ET-3 (3 nmol kg−1, i.v., bolus, maximum response: 30 ± 3 mmHg), SX6b (1 nmol kg−1, i.v., bolus, maximum response: 41 ± 5 mmHg) and SX6c (1 nmol kg−1, i.v., bolus, maximum response: 24 ± 4 mmHg) by 65, 60, 88 and 50%, respectively. 4 With the exception of big ET-1, all the peptides used in this study induced an initial transient depressor response (–32 ±3 mmHg, n = 18). Although BQ-123 (1 mg kg−1, i.v., bolus) did not affect the absolute magnitude of the fall in MAP, the ETA receptor antagonist significantly prolonged the depressor responses induced by ET-3 and SX6b. 5 Thus, BQ-123 attenuates the pressor, but not the depressor effects of ET-1, big ET-1, ET-3, SX6b and SX6c. Complete inhibition of the pressor responses could not be achieved, suggesting that a component of the pressor response is not mediated via the ETA receptor.