Egon Roesch

The effect of cyclic adenosine- and guanosine 3',5'-monophosphate on the normal and drug-increased coronary blood flow.

Abstract Cyclic 3′,5′-AMP (cAMP), cyclic 3′,5′-GMP (cGMP) and their more lipo-phylic derivatives (cDBA, cMBA, cDBG) were studied in conscious, resting dogs prepared with chronically implanted electromagnetic flow probes and catheters. Coronary blood flow (CBF), heart rate, aortic blood pressure and in some cases, cardiac output were recorded. cAMP, cDBA and cMBA increased the normal and pharma-cologically elevated CBF while cGMP and its dibutyryl derivative were without effect. Pretreatment with theophylline, a phosphodiesterase inhibitor, diminished the effect of cAMP but enhanced the effect of cDBA and cMBA. The data suggest that cAMP cannot be considered as a second messenger responsible for the maintenance of coronary vascular tone. It may, however, be responsible for coronary vasodilation.

Effect of Cyclic Nucleosid Phosphates on the Normal and Elevated Myocardial Blood Flow

Cyclic AMP (adenosine 3′, 5′ -monophosphate) and cyclic GMP (guanosine 3′, 5′ -monophosphate) were identified in mammalian tissue several years ago and it was suggested that these hormones might play a role in the reactivity of the smooth muscle of the coronary arteries. The present studies were designed to evaluate the effect of these agents and their more lipophilic derivatives on the normal and elevated coronary blood flow (CBF) of conscious dogs. Elevation of CBF was produced by intravenous injection of metrifudil (Th 322). Various amounts of the cyclophosphates up to 80 mg/dog x min were given by direct intracoronary infusion. The normal and pharmacologically enhanced CBF increased further when cyclic AMP and its dibutyryl derivative (cDBA) were given. The effect of cDBA was augmented after theophylline, whereas the effect of cyclic AMP was diminished after theophylline. This suggests that the increase in CBF by cyclic AMP is mainly due to a contamination by non-cyclic adenosine compounds, e.g. 5′ AMP which is a very potent coronary dilator. Cyclic GMP was without effect. The possible role of the cyclophosphates in the adaptation of CBF to myocardial metabolism will be discussed.