Haemodynamic and cardiac effects of kinin B1 and B2 receptor stimulation in conscious instrumented dogs.
1. Mongrel dogs were chronically instrumented with an intra-aortic catheter, a Königsberg intraventricular pressure transducer and a Döppler flow probe around the left coronary artery. After ganglionic blockade with hexamethonium, the cardiovascular effects of bradykinin B1 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 microgram kg-1 min-1) and des-Arg9-BK (1 microgram kg-1 min-1) 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 B1 receptor antagonist, des-Arg9-[Leu8]-BK (25 micrograms kg-1) 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 micrograms kg-1), only the decreases 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, 45 mg kg-1) 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-1) 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 B1 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 B1 receptors are at least in part coupled to the release of NO.
Bélichard
P
P
Centre de Recherches, Laboratoires Fournier S.C.A., Dijon, France.
Loillier
B
B
Paquet
J L
JL
Luccarini
J M
JM
Pruneau
D
D
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists*; D014655:Vascular Resistance / Q000187:drug effects
D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; D019335:Nitroarginine; D018738:Hexamethonium; D001120:Arginine; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D007213:Indomethacin