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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
Author(s) -
McMurdo Lorraine,
Corder Roger,
Thiemermann Christoph,
Vane John R.
Publication year - 1993
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.1476-5381.1993.tb12840.x
Subject(s) - bolus (digestion) , endocrinology , chemistry , blood pressure , medicine , endothelin receptor , mean arterial pressure , antagonist , endothelin 1 , receptor , heart rate
1 The effects of the ET A 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 ET A 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 ET A receptor.