Adenosine formation during hypoxia in isolated hearts: effect of adrenergic blockade.
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.
Gorman
M W
MW
Department of Physiology, Michigan State University, East Lansing 48823.
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M X
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Sparks
H V
HV
D000241:Adenosine / Q000096:biosynthesis*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus
D010710:Phosphates; D010643:Phenoxybenzamine; D010758:Phosphorus; D001262:Atenolol; D000241:Adenosine; D010646:Phentolamine