Cardiac ischemia, role

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

Mozzicato S, Joshi BV, Jacobson KA, Liang BT (2004) Role of direct RhoA-phospholipase D1 interaction in mediating adenosine-induced protection from cardiac ischemia. FASEB J 18(2) 406 108... 

PetrosiUo, G., Di Venosa, N., Ruggiero, F.M., Pistolese, M., D Agostino, D., Tiravanti, E., Fiore, T., and Paradies, G. 2005. Mitochondrial dysfunction associated with cardiac ischemia/reperfusion can be attenuated by oxygen tension control. Role of oxygen-free radicals and cardiolipin. Biochim. Biophys. Acta 1710 78-86. 

Xiao CY, Hara A, Yuhki K, Fujino T, Ma H, Okada Y, Takahata O, Yamada T, Murata T, Narumiya S, Ushikubi F. Roles of prostaglandin 1(2) and thromboxane A(2) in cardiac ischemia-reperfusion injury a study using mice lacking their respective receptors. Circulation. 104(2001)2210-2215. 

Ischemia-reperfusion is thought to mediate the severe organ dysfunction witnessed after shock or cardiac arrest. HSPs could play a major role in the defence against ischemia-reperfusion injury. Many in vivo experimental models of ischemia and/or ischemia-reperfusion have demonstrated HSP induction. 

Furukawa T, Kimura S, Furukawa N, Bassett AL, Myerburg RJ Role of cardiac ATP-regulated potassium channels in differential responses of endocardial and epicardial cells to ischemia. Circ Res 1991 ... 

Of particular interest is a proof of principle study showing that cardiac-specific overexpression of the A3 receptor can protect the murine myocardium against ischemia/reperfusion (Cross et al. 2002 Black et al. 2002). Although some raised the question that the widely used prototypical agonist Cl-IBMECA (2-chloro-iV6-(3-iodobenzyl)adenosine-5 -/V-methyluronamide) may not be selective at the adenosine A3 receptor in intact heart, Cl-IBMECA could not exert a cardio-protective effect in A3R-knockout mice, pointing to an essential role of the A3 receptor in... 

Booz, G.W., Day, J.N.E., and Baker, K.M. 2002. Interplay between the cardiac renin angiotensin system and JAK-STAT signaling Role in cardiac hypertrophy, ischemia/reperfusion dysfunction, and heart failure. J. Mol. Cell. Cardiol. 34 1443-1453. 

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