Mediation by B₁ and B₂ receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs

Abstract

1 Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des-Arg9-BK, a selective B, kinin receptor agonist, were characterized following i.v. pretreatment with selective B, ([Leu8]-des-Arg9-BK) and B2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2 Des-Arg9-BK (0.05-3.3 nmol kg-') produced dose-dependent decreases in mean arterial blood pressure with a ED_0 0.4 nmol kg-'. The vasodepressor effects evoked by des-Arg9-BK (0.6 nmol kg-') and BK (0.2 nmol kg-') were greater after i.v. and i.a. injections, respectively. 3 The vasodepressor response to BK (0.6 nmol kg-') but not to des-Arg9-BK (0.6 nmol kg-') was significantly (P<0.001) blocked by pretreatment with the B2 receptor antagonist, Hoe 140. 4 The vasodepressor response to des-Arg9-BK (0.6 nmol kg-') but not to BK (0.6 nmol kg-') was significantly (P<0.001) reduced by pretreatment with the selective B, receptor antagonist, [Leu8]-desArg9-BK. Although both B, and B2 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-', i.v.) but not that to BK or des-Arg9-BK (0.6 nmol kg-').6 These results suggest, firstly, that the vasodepressor responses to i.v. BK and des-Arg9-BK are mediated by the activation of B2 and B, 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, receptors in canine cardiovascular homeostasis.

Enhanced Blood Pressure Sensitivity to Deoxycorticosterone in Mice With Disruption of Bradykinin B 2 Receptor Gene

“…25 In addition, residual agonist effects of icatibant have been reported in the rat. 26 Therefore, caution is appropriate when the hypertensive effect induced by icatibant is attributed to selective blockade of the B 2 receptor. However, consistent with the evidence provided by the use of the antagonist is the report that Brown Norway Katholiek rats, a strain congenitally deficient in kininogen in plasma and devoid of kinin release in urine, exhibit a more rapid BP increase during DOC-salt treatment than normal Brown Norway Kitasato rats.…”

Stimulation of Bradykinin B 1 Receptors Induces Vasodilation in Conductance and Resistance Coronary Vessels in Conscious Dogs

“…7 B 1 receptors are constitutively and functionally expressed in the arterial vessels and glomerulus of rats, 8,9 in the pulmonary vascular bed of cats, 10 and in the arterial vessels of pigs 11 and dogs. [12][13][14] In humans, a recent in vitro study using immunolabeling techniques revealed the presence of B 1 receptors in vascular endothelial and smooth muscle cells of large elastic arteries, muscular arteries (such as coronary arteries), and muscular arterioles. 15 The functional role of constitutive B 1 receptors in the arterial vessels of dogs is well documented.…”

“…15 The functional role of constitutive B 1 receptors in the arterial vessels of dogs is well documented. [12][13][14] The stimulation of these receptors produces a vasorelaxation and a reduction in blood pressure. [12][13][14] However, their physiological implications in the coronary circulation remain to be determined.…”

“…[12][13][14] The stimulation of these receptors produces a vasorelaxation and a reduction in blood pressure. [12][13][14] However, their physiological implications in the coronary circulation remain to be determined. Therefore, the present study was designed to examine, in conscious dogs, the coronary effects of B 1 receptor stimulation and the mechanisms involved.…”

Renal Protective Role of Bradykinin B1 Receptor in Stroke-Prone Spontaneously Hypertensive Rats

“…B1R-mediated hypotensive responses have been demonstrated and characterized in the rabbit (24), rat (25), pig (29) and dog (30). Although those studies were carried out under inflammatory conditions, their respective authors suggested that early decrease in mean arterial pressure is due to an acute decrease in peripheral vascular resis-…”