ADENOSINE FORMATION DURING HYPOXIA IN ISOLATED HEARTS - EFFECT OF ADRENERGIC-BLOCKADE

Adrenergic receptor blockade has been reported to decrease cardiac ade nosine formation and release during hypoxia. We wished to determine wh ether this occurs by an improvement in the energy supply/demand ratio. Isolated guinea pig hearts were perfused at a constant pressure of 50 mm Hg. Hypoxia (30% O-2) was maintained for 20 min while adenosine re lease and venous PO2 were measured in the coronary venous effluent. be ta-adrenergic blockade with 5 mu M atenolol did not change hypoxic ade nosine release (Control: 15.6+/-2.7, Atenolol: 23.6+/-5.7 nmol/g/20 mi n). Addition of 6 mu M phentolamine with atenolol significantly reduce d hypoxic adenosine release (4.4+/-1.4 nmol/g/20 min, P<0.05). Atenolo l was without hemodynamic effects, but addition of phentolamine reduce d left ventricular pressure development, heart rate, and oxygen consum ption prior to hypoxia. Atenolol plus phentolamine did not change veno us PO2 during hypoxia. Treatment with phenoxybenzamine (1 mu M) plus a tenolol also reduced adenosine release (7.4+/-0.8 nmol/g/20 min). Cont rol experiments and atenolol plus phentolamine experiments were repeat ed using P-31-NMR to measure high energy phosphates. Adrenergic blocka de had no effect on phosphate concentrations during normoxia, but resu lted in higher [PCr], lower [P-i] and higher phosphorylation potential s during hypoxia. Adrenergic blockade also prevented the hypoxia-induc ed rise in intracellular [H+], [AMP] and [ADP] seen in control hearts. The changes in phosphorylation potential are correlated with similar changes in adenosine release in adrenergically intact hearts. We concl ude that the primary effect of adrenergic blockade during hypoxia is a reduction in ATP use due to alpha-receptor blockade. This leads to im proved high energy phosphate concentrations during hypoxia and a reduc tion in adenosine formation.