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.