CONTRIBUTION OF CALCIUM TO ISOPROTERENOL-STIMULATED LIPOLYSIS IN THE ISOLATED-PERFUSED RABBIT HEART

The present study was performed to investigate the contribution of ade nosine 3',5'-cyclic monophosphate (cAMP and calcium to isoproterenol-s timulated lipolysis in the isolated rabbit heart perfused with Krebs-H enseleit buffer according to the method of Langendorff. Isoproterenol (0.05-1.5 nmol) increased glycerol output, left ventricular dP/dt(max) , and heart rate but decreased coronary perfusion pressure. The phosph odiesterase inhibitor 3-isobutyl-1-methylxanthine (50 muM) failed to a lter the basal or isoproterenol-induced increase in glycerol output, w hereas cilostamide (5 muM) enhanced basal and inhibited isoproterenol- stimulated glycerol output. Inhibition of adenylyl cyclase with (pheny lisopropyl)adenosine reduced isoproterenol-stimulated mechanical param eters but had no effect on basal or isoproterenol-stimulated glycerol output, whereas the cAMP analogue 8-(4-chlorophenylthio)-cAMP did not increase glycerol output but produced changes in mechanical parameters similar to isoproterenol. Decreasing perfusion fluid calcium concentr ation from 1.2 to 0.5 mM or infusion of the calcium channel antagonist diltiazem (23 muM) abolished the increase in glycerol output in respo nse to isoproterenol. Activation of adenylyl cyclase with forskolin in creased glycerol output, but the increase was abolished by reducing pe rfusion fluid calcium concentration or by diltiazem. These data sugges t that, in the rabbit heart, isoproterenol-stimulated lipolysis appear s to be mediated predominantly by calcium as a secondary metabolic res ponse provided by the increase in mechanical activity.