PRAZOSIN REDUCES MYOCARDIAL-ISCHEMIA REPERFUSION-INDUCED CA2-HEART BYINHIBITING PHOSPHOINOSITIDE SIGNALING( OVERLOADING IN RAT)

The aim of this study was to establish whether or not alpha(1)-adrener gic receptors are implicated in triggering phosphoinositide hydrolysis and intracellular Ca2+ accumulation during myocardial ischemia and re perfusion. In isolated perfused rat hearts, the selective alpha(1)-rec eptor antagonist prazosin abolished the increase in radioactivity inco rporation into cellular inositol phosphates induced by 30 min ischemia followed by 30 min reperfusion, and selectively blocked the degradati on of phosphoinositides; only minor changes in the ischemia/reperfusio n-induced loss of other classes of phospholipids were seen. In additio n, a prazosin-induced decrease of ischemia/reperfusion Ca2+ overloadin g was documented in real-time recordings of epicardial cytosolic free Ca2+ in fura 2-loaded hearts. An inhibition of early ischemic Ca2+ ris e was observed, as well as a lower peak of cytosolic free Ca2+ and a m ore rapid reversal to normal values during reperfusion. Moreover, alph a(1)-adrenergic blockade resulted in a significant improvement in the recovery of myocardial function during reperfusion: an increased left ventricular developed pressure and maximum rate of rise of systolic pr essure paralleled the decrease in time-averaged cytosolic Ca2+ and the increase in amplitude of Ca2+ transients, respectively. It is conclud ed that myocardial Ca(2+)overloading during ischemia and reperfusion m ay be triggered by alpha(1)-adrenergic receptor-induced polyphosphoino sitide hydrolysis.