LUSITROPIC EFFECTS OF ALPHA-ADRENERGIC AND BETA-ADRENERGIC STIMULATION IN AMPHIBIAN HEART

The effects of beta and alpha-adrenergic stimulation in amphibian supe rfused hearts and ventricular strips were studied. Superfusion with 3 x 10(-8) M isoproterenol produced a positive inotropic effect, as dete cted by a 92 +/- 24% increase in the maximal rate of contraction (+T) and a positive lusitropic effect characterized by a decrease in both t he ratio +T/-T (23 +/- 5%) and the half relaxation time (t(1/2)) (19 /- 4%). The mechanical behavior induced by the beta-agonist was associ ated with an increase in the intracellular cAMP levels from control va lues of 173 +/- 19 to 329 +/- 28 nmol/mg wet tissue. Hearts superfused with P-32 in the presence of isoproterenol showed a significant incre ase in Tn 1 phosphorylation (from 151 +/- 13 to 240 +/- 44 pmol P-32/m g MF protein) without consistent changes in phosphorylation of C-prote in. In sarcoplasmic reticulum membrane vesicles, no phospholamban phos phorylation was detected either by beta-adrenergic stimulation of supe rfused hearts or when phosphorylation conditions were optimized by dir ect treatment of the vesicles with cAMP-dependent protein kinase (PKA) and [y P-32] ATP. The effect of alpha-adrenergic stimulation on ventr icular strips was studied at 30 and 22 degrees C. At 30 degrees C, the effects of 10(-5) to 10(-4)M phenylephrine on myocardial contraction and relaxation were diminished to non significant levels by addition o f propranolol. At 22 degrees C, blockage with propranolol left a reman ent positive inotropic effect (10% of the total effect of phenylephrin e) and changed the phenylephrine-induced positive lusitropic effect in to a negative lusitropic action. These propranolol-resistant effects w ere abolished by prazosin. Our results suggest that in amphibian heart , both the inotropic and lusitropic responses to catecholamines are ma inly due to a beta-adrenergic stimulation which predominates over the alpha-adrenergic response. Phospholamban phosphorylation seems not to be involved in mediating the positive lusitropic effect of beta-adrene rgic agents whereas phosphorylation of troponin I may play a critical role.