Haemodynamic and cardiac effects of kinin B₁ and B₂ receptor stimulation in conscious instrumented dogs

Abstract

1 Mongrel dogs were chronically instrumented with an intra-aortic catheter, a K6nigsberg intraventricular pressure transducer and a D6ppler flow probe around the left coronary artery. After ganglionic blockade with hexamethonium, the cardiovascular effects of bradykinin B, and B2 receptor agonists, des-Arg9-bradykinin and bradykinin (BK), were investigated in the presence and absence of specific antagonists. The contribution of nitric oxide (NO) and prostanoids to the cardiovascular effects of kinins was also examined. 2 BK (1 gg kg-' min-') and des-Arg9-BK (1 Mug kg-' min-') both given as a 2 min i.v. infusion, produced a significant decrease in mean arterial pressure (MAP, -34+4% for BK and -45+2% for des-Arg9-BK) and coronary vascular resistance (CVR, -37+5% for BK and -50+2% for des-Arg9-BK), without affecting cardiac contractility, left ventricular end diastolic pressure, and coronary velocity. BK caused a significantly greater decrease in MAP and CVR than des-Arg9-BK (P<0.05). 3 Pretreatment with the B, receptor antagonist, des-Arg9-[Leu8]-BK (25 pg kg-') significantly inhibited the decrease in MAP and CVR produced by des-Arg9-BK but not by BK. Infusion of des-Arg9-[Leu8]-BK alone also induced a significant decrease in MAP and CVR (P<0.05). In the presence of the B2 receptor antagonist, Hoe 140 (25 jug kg-'), only the decreases in MAP and CVR caused by BK were significantly reduced (P<0.05). 4 Inhibition of NO synthase with Nw-nitro-L-arginine (L-NOARG, 45 mg kg-') significantly (P<0.05) prevented the decrease in CVR but not MAP induced by des-Arg9-BK, whilst responses to BK were not affected by L-NOARG pretreatment. Inhibition of prostanoid synthesis with indomethacin (25 mg kg-') did not affect the reductions in MAP and CVR induced by des-Arg9-BK or BK. 5 In conclusion, i.v. des-Arg9-BK and BK administration induced reductions in MAP and CVR suggesting that in conscious instrumented dogs both B, and B2 receptors are present and can affect systemic blood pressure and coronary resistance regulation. Our results also suggest that prostanoids are not involved in the vascular response to kinins and that coronary vascular B, receptors are at least in part coupled to the release of NO.

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

“…The coronary effects of des-Arg 9 -bradykinin on conductance and resistance vessels were prevented by LNA, indicating that the effects of des-Arg 9 -bradykinin are, in a large part, mediated by NO, which is consistent with a previous study in which NO synthase inhibitors and des-Arg 9 -bradykinin were administrated intravenously. 13 In vitro, the bradykinin-induced vasorelaxation is potentiated by ACE inhibitors. 24 In humans, bradykinin is involved in the vascular effect of ACE inhibitors.…”

“…10 In dogs, B 1 receptors are also present in the isolated renal artery and mediate vasorelaxation, 12 and in intact preparations, B 1 receptor stimulation by des-Arg 9 -bradykinin produces a hypotensive effect. 13,14 By use of a specific antibody directed to the peptide sequences of B 1 receptors, it has recently been shown in humans that B 1 receptors are present not only in vascular endothelial and smooth muscle cells of large elastic arteries but also in muscular arteries, such as coronary arteries and muscular arterioles. 15 The notion that B 1 receptors are constitutively expressed in coronary vessels is supported by the present study, which shows the functional coronary effects of des-Arg 9 -bradykinin in the absence of evidence of inflammation by blood analysis.…”

“…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.…”