HEMODYNAMIC AND CARDIAC EFFECTS OF KININ B-1 AND B-2 RECEPTOR STIMULATION IN CONSCIOUS INSTRUMENTED DOGS

1 Mongrel dogs were chronically instrumented with an intra-aortic cath eter, a Konigsberg intraventricular pressure transducer and a Doppler flow probe around the left coronary artery. After ganglionic blockade with hexamethonium, the cardiovascular effects of bradykinin B-1 and B -2 receptor agonists, des-Arg(9)-bradykinin and bradykinin (BK), were investigated in the presence and absence of specific antagonists. The contribution of nitric oxide (NO) and prostanoids to the cardiovascula r effects of kinins was also examined. 2 BK (1 mu g kg(-1) min(-1)) an d des-Arg(9)-BK (1 mu g kg(-1) min(-1)) both given as a 2 min i.v. inf usion, produced a significant decrease in mean arterial pressure (MAP, -34+/-4% for BK and -45+/-2% for des-Arg(9)-BK) and coronary vascular resistance (CVR, -37+/-5% for BK and -50+/-2% for des-Arg(9)-BK), wit hout affecting cardiac contractility, left ventricular end diastolic p ressure, and coronary velocity. BK caused a significantly greater decr ease in MAP and CVR than des-Arg(9)-BK (P<0.05). 3 Pretreatment with t he B-1 receptor antagonist. des-Arg(9)-[Leu(8)]-BK (25 mu g kg(-1)) si gnificantly inhibited the decrease in MAP and CVR produced by des-Arg( 9)-BK but not by BK. Infusion of des-Arg(9)-[leu(8)]-BK alone also ind uced a significant decrease in MAP and CVR (P<0.05). In the presence o f the B-2 receptor antagonist. Hoe 140 (25 mu g kg(-1)), only the decr eases in MAP and CVR caused by BK were significantly reduced (P<0.05). 4 Inhibition of NO synthase with N-omega-nitro-L-arginine (L-NOARG; 4 5 mg kg(-1)) significantly (P<0.05) prevented the decrease in CVR but not MAP induced by des-Arg(9)-BK, whilst responses to BK were not affe cted by L-NOARG pretreatment. Inhibition of prostanoid synthesis with indomethacin (25 mg kg(-1)) did not affect the reductions in MAP and C VR induced by des-Arg(9)-BK or BK. 5 In conclusion, i.v. des-Arg(9)-BK and BK administration induced reductions in MAP and CVR suggesting th at in conscious instrumented dogs both B-1 and B-2 receptors are prese nt and can affect systemic blood pressure and coronary resistance regu lation. Our results also suggest that prostanoids are not involved in the vascular response to kinins and that coronary vascular B-1 recepto rs are at least in part coupled to the release of NO.