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 elicited by angiotensin-converting enzyme (ACE) inhibition is isolated guinea pig heart performing pressure-volume work. Cardiac output (CO), coronary blood flow (CBF), and external heart work (EHW) were determined before and after ischemia and reperfusion (15 min each). Furthermore, the 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 throughout the experiment improved postischemic function significantly (55% recovery of EHW for 25 microM RT vs. 30% for controls). RT was cardioprotective 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, respectively). The BK2-receptor antagonist HOE 140 (10 nM) inhibited the RT effect and attenuated the effect of 1 nM BK. Total CBF during reperfusion, lactate production, intracellular levels of GSH, and release of oxidized GSH (GSSG) did not differ among the groups. In contrast, release of reduced GSH during the first 5 min of reperfusion was considerably influenced by pharmacologic intervention, correlating inversely with postischemic heart function. Coapplication of Hoe 140 prevented the changes in GSH release. Our results demonstrate that BK, formed endogenously in the heart, is responsible for cardioprotection by the ACE inhibitor RT in isolated guinea pig heart and decreases GSH release during reperfusion. The exact mechanisms leading to hemodynamic improvement and metabolic changes by BK remain unclear.
Massoudy
P
P
Department of Physiology, University of Munich, Germany.
Becker
B F
BF
Gerlach
E
E
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000378:metabolism; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007773:Lactates; D019344:Lactic Acid; D000244:Adenosine Diphosphate; C052549:ramiprilat; D000255:Adenosine Triphosphate; D005978:Glutathione; D017257:Ramipril; D001920:Bradykinin