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Mediation by B 1 and B 2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs
Author(s) -
Nakhostine Nabil,
Ribuot Christophe,
Lamontagne Daniel,
Nadeau Réginald,
Couture Réjean
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.tb13773.x
Subject(s) - bradykinin , kinin , chemistry , endocrinology , medicine , receptor , antagonist , agonist , receptor antagonist , bradykinin receptor , prostaglandin , pharmacology
1 Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des‐Arg 9 ‐BK, a selective B 1 kinin receptor agonist, were characterized following i.v. pretreatment with selective B 1 ([Leu 8 ]‐des‐Arg 9 ‐BK) and B 2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2 Des‐Arg 9 ‐BK (0.05–3.3 nmol kg −1 ) produced dose‐dependent decreases in mean arterial blood pressure with a ED 50 0.4 nmol kg −1 . The vasodepressor effects evoked by des‐Arg 9 ‐BK (0.6 nmol kg −1 ) and BK (0.2 nmol kg −1 ) were greater after i.v. and i.a. injections, respectively. 3 The vasodepressor response to BK (0.6 nmol kg −1 ) but not to des‐Arg 9 ‐BK (0.6 nmol kg −1 ) was significantly ( P < 0.001) blocked by pretreatment with the B 2 receptor antagonist, Hoe 140. 4 The vasodepressor response to des‐Arg 9 ‐BK (0.6 nmol kg −1 ) but not to BK (0.6 nmol kg −1 ) was significantly ( P < 0.001) reduced by pretreatment with the selective B 1 receptor antagonist, [Leu 8 ]‐des‐Arg 9 ‐BK. Although both B 1 and B 2 receptor antagonists caused a transient fall in blood pressure, their inhibitory action was unlikely to be related to a desensitization mechanism. 5 Inhibition of prostaglandin synthesis with indomethacin prevented the vasodepressor response induced by arachidonic acid (1 mg kg −1 , i.v.) but not that to BK or des‐Arg 9 ‐BK (0.6 nmol kg −1 ). 6 These results suggest, firstly, that the vasodepressor responses to i.v. BK and des‐Arg 9 ‐BK are mediated by the activation of B 2 and B 1 receptors, respectively; secondly, that prostaglandins are not involved in the vasodepressor responses to kinins. These findings provide pharmacological evidence for the existence of functionally active B 1 receptors in canine cardiovascular homeostasis.