CORONARY AUTOREGULATION AND PURINE RELEASE IN NORMOXIC HEART AT VARIOUS CYTOPLASMIC PHOSPHORYLATION POTENTIALS - DISPARATE EFFECTS OF ADENOSINE

The impacts of energy-yielding substrates on coronary flow autoregulation, cytoplasmic phosphorylation potential {[ATP]/([ADP][P(i)])} and purine nucleoside production were studied in Langendorff-perfused guinea pig hearts. The perfusion medium was substrate-free or contained glucose alone or in combination with pyruvate, lactate, acetate, or octanoate as fatty acid. When coronary flow was adjusted for myocardial oxygen consumption, only pyruvate supported near-perfect intrinsic autoregulation at highly sustained [ATP]/([ADP][P(i)]) and low interstitial adenosine concentrations ([Ado]). In contrast, hearts perfused with substrate-free medium were deenergized at very high [Ado], especially at supraphysiological pressures, which markedly impaired autoregulatory vasoconstriction. Thus, efficient autoregulatory vasoconstriction was associated with high [ATP]/([ADP\[P(i)]) at low [Ado]. On the other hand, autoregulatory vasodilation at subphysiological pressures was associated with increased [Ado] and partially blocked by 28-mu-M theophylline demonstrating (partial) adenosine mediation. Massive accumulation of IMP, especially relative to free cytoplasmic AMP, occurred at normal intracellular pH during myocyte deenergization by substrate-free perfusion. This may indicate allosteric activation of native AMP deaminase in situ, perhaps because of collapse of [ATP]/([ADP][P(i)]). Similarly, rates of adenosine plus inosine release and of total purines, also including urate, exhibited non-linear sigmoidal rather than linear or rectangular hyperbolic dependences on free cytoplasmic AMP concentration (not total AMP content). Since inclusion of IMP as a co-variable of free AMP appreciably improved the sigmoidal fits, IMP appeared to be a significant precursor of released inosine in guinea pig heart.