Adrenergic receptor blockade has been reported to decrease cardiac
adenosine formation and release during
hypoxia. We wished to determine whether 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% O2) was maintained for 20 min while
adenosine release and venous PO2 were measured in the coronary venous effluent. beta-
adrenergic blockade with 5 microM
atenolol did not change hypoxic
adenosine release (Control: 15.6 +/- 2.7,
Atenolol: 23.6 +/- 5.7 nmol/g/20 min). Addition of 6 microM
phentolamine with
atenolol significantly reduced hypoxic
adenosine release (4.4 +/- 1.4 nmol/g/20 min, P < 0.05).
Atenolol was without hemodynamic effects, but addition of
phentolamine reduced left ventricular pressure development, heart rate, and oxygen consumption prior to
hypoxia.
Atenolol plus
phentolamine did not change venous PO2 during
hypoxia. Treatment with
phenoxybenzamine (1 microM) plus
atenolol also reduced
adenosine release (7.4 +/- 0.8 nmol/g/20 min). Control experiments and
atenolol plus
phentolamine experiments were repeated using 31P-NMR to measure high energy
phosphates.
Adrenergic blockade had no effect on
phosphate concentrations during normoxia, but resulted in higher [PCr], lower [P(i)] and higher phosphorylation potentials during
hypoxia.
Adrenergic blockade also prevented the
hypoxia-induced 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 conclude that the primary effect of
adrenergic blockade during
hypoxia is a reduction in
ATP use due to alpha-receptor blockade. This leads to improved high energy
phosphate concentrations during
hypoxia and a reduction in
adenosine formation.