Bradykinin-mediated metabolic effects in isolated perfused rat hearts.
Bradykinin perfusion (BK 1 x 10(-12) to 1 x 10(-8) mol/l) of isolated working rat hearts with postischemic reperfusion arrhythmias induced a reduction of the incidence as well as duration of ventricular fibrillation, improvement of cardiodynamics via increased left ventricular pressure, contractility, and coronary flow without changes in heart rate. These beneficial effects were accompanied by reduced activities of the cytosolic enzymes lactate dehydrogenase and creatine kinase as well as lactate output. In the myocardial tissue lactate content was reduced and the energy rich phosphates increased compared to saline perfused control hearts. Glycogen stores were also preserved. These beneficial effects of BK were concentration-dependently abolished by perfusion of the B2 kinin receptor antagonist HOE 140 and the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). These results suggest that improved cardiac function during and after myocardial ischemia as well as increased energy rich phophates and glycogen stores are mediated by BK and the subsequent release of NO, shifting myocardial metabolism during ischemia and reperfusion to the glucose pathway which leads to changes indicative for cardioprotection.
Schoelkens
B A
BA
Hoechst AG, Frankfurt/Main, Germany.
Linz
W
W
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019335:Nitroarginine; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007773:Lactates; D010725:Phosphocreatine; D019335:Nitroarginine; C065679:icatibant; D000255:Adenosine Triphosphate; D006003:Glycogen; D001120:Arginine; D001920:Bradykinin