A factor released from coronary vascular endothelium inhibits myocardial contractile performance.
The effect of continuous intracoronary infusion of bradykinin (BK; 10(-6) M) on the myocardial contractile performance of isolated Langendorff-perfused ferret hearts was investigated. BK produced a transient but marked inhibition of contractile performance, the changes being fully resolved by 2-3 min. This effect of BK was blocked after disruption of the coronary vascular endothelium with Triton X-100 (0.5%). Prior infusion of the endothelium-derived relaxing factor (EDRF) synthesis inhibitor N omega-nitro-L-arginine (10(-4) M) failed to alter the mechanical effects induced by BK. These changes in contractile performance were reduced, however, by the K+ channel-blocking agent glibenclamide (10(-6) M) but were unaffected by tetrapentylammonium bromide (5 x 10(-5) M) or 4-aminopyridine (10(-3) M). These findings therefore indicate that BK inhibits myocardial contractile performance by opening myocardial ATP-sensitive K+ channels, probably via the release of an endothelium-derived factor unrelated to EDRF.
Fort
S
S
Department of Pharmacology, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
Lewis
M J
MJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005289:Ferrets; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology
D019335:Nitroarginine; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D017830:Octoxynol; D001120:Arginine; D001920:Bradykinin; D005905:Glyburide