Effects of exogenous adenosine 3',5'‐monophosphate in man: I. Cardiovascular responses

Abstract

The cardiovascular response to administration of cyclic adenosine 3',5'‐monophosphate (3',5'‐AMP) was studied in 26 human volunteers. In relatively large doses (10 mg. per kilogram or 0.5 mg. per kilogram per minute), 3',5'‐AMP induced prompt cardioacceleration and increased cardiac output. In contrast to those receiving rapid 3',5'‐AMP iniection, all subiects receiving a constant infusion of the nucleotide showed a progressive and sustained elevation of systolic blood pressure. Responses to 3',5'‐AMP were demonstrated in the presence of attempts at pharmacologic blockade of beta adrenergic and cholinergic receptor sites by dl‐propranolol and atropine, respectively. Following production of marked hypotension by trimethaphan (Arfonad) and glyceryl trinitrate, with consequent blockade of sympathetically induced cardioacceleration, administration of 3',5'‐AMP promptly increased heart rate without any change in blood pressure. These findings suggested a direct cardiac action of the nucleotide rather than reflex alterations of the heart due to arterial pressure changes. The cardiac findings in man support in vitro data that 3',5'‐AMP may represent part of the biochemical basis for the myocardial response to catecholamines.