CARDIOVASCULAR AND METABOLIC EFFECTS OF CYCLIC ADENOSINE 3', 5'-MONOPHOSPHATE IN UNANESTHETIZED DOGS

¹ United States Army Medical Research and Nutrition Laboratory, Fitzsimons General Hospital, Denver, Colorado

3', 5'-AMP was studied in fed and fasted, unanesthetized dogs prepared with catheters chronically implanted in the right atrium and aortic arch. Determinations of heart rate, cardiac output, mean blood pressure, total peripheral resistance, stroke volume, pulse pressure, blood glucose and plasma FFA were recorded. The actions of 3', 5'-AMP mimicked those of catecholamines, as reflected by an increase in heart rate, cardiac output and blood glucose. Following single intracardiac doses of 3', 5'-AMP (4-8 mg/kg), heart rate increased within seconds. Although there was a slower, transient decrease in mean blood pressure, heart rate remained significantly elevated for 30 min, and initially did not appear to be an indirect reflex action compensatory to the decline in blood pressure. Blood glucose increased to a maximum at 7 min and then decreased, while plasma FFA continuously decreased for 15 min. No significant cardiac or metabolic changes followed administration of 2', 3'-AMP, 5'-AMP, ATP or saline. Prior treatment with DCI prevented the cardiovascular but not the metabolic effects of 3’, 5’-AMP. This was probably due to the observed agonist chronotropic action of DCI which prevented further cardioacceleration by 3’, 5’-AMP. pretreatment with inderal failed to block either the cardiovascular or metabolic effects of 3’, 5’-AMP, which suggests that the cyclic nucleotide does not act via cardiac beta adrenergic receptor stimulation per se, but probably has its pharmacologic effect beyond the beta-receptor site. Pretreatment with theophylline or imidazole did not alter the cardiac responses to 3', 5'-AMP. The significance of the cardiovascular actions of 3', 5'-AMP demonstrated in dogs as related to the hypothesis obtained from in vitro data that 3', 5'-AMP may mediate catecholamine-induced effects on heart contraction is discussed.