guanosine-diphosphate and Coronary-Disease

Langendorff perfused rat hearts show synchronous, statistically significant, systematic variations in ATP and ADP. Here we show that AMP and IMP also vary in register with ATP and ADP and we suggest that the synchronizing trigger for these oscillations may be ischaemia. Oscillations in the ATP/ADP ratio were found to be significantly correlated with creatine phosphate content but by contrast these quantities vary quite differently from the GTP/GDP ratio. Cyclic GMP oscillations showed a significant negative correlation with variations in ADP. Epinephrine raised mean cyclic AMP content and stabilized cyclic GMP oscillations, but had little other effect on the purine nucleotide variations.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Coronary Disease; Cyclic AMP; Cyclic GMP; Epinephrine; Guanosine Diphosphate; Guanosine Triphosphate; Heart; Inosine Monophosphate; Kinetics; Male; Myocardium; Perfusion; Purine Nucleotides; Rats; Rats, Inbred Strains

It is a characteristic feature of the myocardium that the derangement in function [6] and the depletion of the ATP pool [1, 2, 9] that occur subsequent to oxygen deficiency persist when blood flow is restored. Of renewed interest is the inability of the heart to replenish rapidly its adenine nucleotide pool once it has been diminished during a brief period of regional ischemia [2, 9]. A hypothesis that could explain this metabolic insufficiency of the myocardium is that the biosynthesis of adenine nucleotides is very slow in the normal heart and is increased only moderately during postischemic recovery [15] so that the replenishment of adenine nucleotides is not affected appreciably. To substantiate such a hypothesis it is necessary to provide evidence that the restitution of the ATP pool can be accelerated by stimulation of this biosynthetic process. In previous studies ribose has been recognized as a substrate that enhances markedly adenine nucleotide biosynthesis in the rat heart [11, 12]. We now demonstrate that continuous i.v. infusion of ribose during recovery from a 15-min period of myocardial ischemia in rats leads to restoration of the cardiac ATP pool within 12 h, whereas 72 h are needed for ATP normalization without any intervention.

Topics: Adenosine Triphosphate; Animals; Coronary Disease; Energy Metabolism; Guanosine Diphosphate; Heart; Myocardium; Pentose Phosphate Pathway; Rats; Ribose; Time Factors