BRADYKININ ACCOUNTS FOR IMPROVED POSTISCHEMIC FUNCTION AND DECREASED GLUTATHIONE RELEASE OF GUINEA-PIG HEART TREATED WITH THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR RAMIPRILAT

We investigated the role of bradykinin (BK) in cardioprotection elicit ed by angiotensin-converting enzyme (ACE) inhibition in isolated guine a pig heart performing pressure-volume work. Cardiac output (CO), coro nary blood flow (CBF), and external heart work (EHW) were determined b efore and after ischemia and reperfusion (15 min each). Furthermore, t he glutathione (GSH) content of hearts and the release of glutathione in coronary venous effluent were measured, as was lactate production. Addition of the ACE-inhibitor ramiprilat (RT) to the perfusate through out the experiment improved postischemic function significantly (55% r ecovery of EHW for 25 muM RT vs. 30% for controls). RT was cardioprote ctive even if only given at onset of reperfusion (50% recovery). BK (0 .1 and 1 nM) was similarly beneficial (55 and 76% recovery of EHW, res pectively). The BK2-receptor antagonist HOE 140 (10 nM) inhibited the RT effect and attenuated the effect of 1 nM BK. Total CBF during reper fusion, lactate production, intracellular levels of GSH, and release o f oxidized GSH (GSSG) did not differ among the groups. In contrast, re lease of reduced GSH during the first 5 min of reperfusion was conside rably influenced by pharmacologic intervention, correlating inversely with postischemic heart function. Coapplication of Hoe 140 prevented t he changes in GSH release. Our results demonstrate that BK, formed end ogenously in the heart, is responsible for cardioprotection by the ACE inhibitor RT in isolated guinea pig heart and decreases GSH release d uring reperfusion. The exact mechanisms leading to hemodynamic improve ment and metabolic changes by BK remain unclear.