BRADYKININ AND ENDOTHELIAL-CARDIAC MYOCYTE INTERACTIONS IN ISCHEMIC PRECONDITIONING

Myocardial ischemia results in the release of a variety of vasoactive substances from coronary vascular endothelial cells and/or from cardia c myocytes. Some of these substances appear to be protective and inclu de nitric oxide and bradykinin. One hypothesis for the pronounced anti arrhythmic effects of preconditioning involves the early generation of bradykinin and, subsequently, nitric oxide. Evidence for early bradyk inin release has come from clinical studies involving patients undergo ing coronary angioplasty where, in 4 of 5 patients, there was evidence for elevated kinin levels in coronary sinus blood either during ballo on inflation (i.e., ischemia) or deflation (reperfusion), The levels r eached are sometimes considerable (increases 10-20 fold). The second p iece of evidence comes from dogs subjected to a preconditioning stimul us (2 x 5 min periods of ischemia), followed 20 min later by occlusion of the same artery for a 25-min period. This preconditioning procedur e markedly reduces ischemia-induced ventricular arrhythmias and, altho ugh under resting conditions there was little difference between arter ial and coronary sinus bradykinin levels (125 +/- 22 and 157 +/- 41 pg /mL, respectively), there was a marked increase in coronary sinus leve ls in preconditioned dogs before the prolonged occlusion (637 +/- 293 pg/mL compared with 114 +/- 18 pg/mL in nonpreconditioned dogs); level s at the end of the prolonged occlusion in the preconditioned dogs wer e also higher (577 +/- 305 pg/mL compared with 162 +/- 34 pg/mL in con trol dogs), Other evidence for the involvement of bradykinin and nitri c oxide comes from studies in which the generation, or effects, of the se mediators have been suppressed (e.g., with the bradykinin B-2 recep tor blocking agent icatibant, with inhibitors of the L-arginine-nitric oxide pathway, and by methylene blue). The conclusion is that early b radykinin release is protective under conditions of ischemia, is presu mably enhanced during therapy with angiotensin-converting enzyme (ACE) inhibitors and is suppressed under conditions of endothelial dysfunct ion. (C) 1997 by Excerpta Medica, Inc.