Contribution of calcium to isoproterenol-stimulated lipolysis in the isolated perfused rabbit heart.

The present study was performed to investigate the contribution of adenosine 3',5'-cyclic monophosphate (cAMP) and calcium to isoproterenol-stimulated lipolysis in the isolated rabbit heart perfused with Krebs-Henseleit buffer according to the method of Langendorff. Isoproterenol (0.05-1.5 nmol) increased glycerol output, left ventricular dP/dtmax, and heart rate but decreased coronary perfusion pressure. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (50 microM) failed to alter the basal or isoproterenol-induced increase in glycerol output, whereas cilostamide (5 microM) enhanced basal and inhibited isoproterenol-stimulated glycerol output. Inhibition of adenylyl cyclase with (phenylisopropyl)adenosine reduced isoproterenol-stimulated mechanical parameters 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 concentration from 1.2 to 0.5 mM or infusion of the calcium channel antagonist diltiazem (23 microM) abolished the increase in glycerol output in response to isoproterenol. Activation of adenylyl cyclase with forskolin increased glycerol output, but the increase was abolished by reducing perfusion fluid calcium concentration or by diltiazem. These data suggest that, in the rabbit heart, isoproterenol-stimulated lipolysis appears to be mediated predominantly by calcium as a secondary metabolic response provided by the increase in mechanical activity.