Cardiopulmonary pharmacology of enkephalins in the conscious dog

Various enkephalins (ENK) have been reported to alter heart rate, systemic blood pressure, and respiratory function but with variable results. We previously found that pentobarbital anesthesia reversed the increases in heart rate and systemic arterial blood pressure produced by Leu5-ENK in the dog. We have now studied the cardiopulmonary responses to systemically injected enkephalins in the awake, chronically instrumented dog. In these unanesthetized dogs, Leu5-ENK, Met5-ENK, and an ENK dimer increased heart rate, systemic arterial pressure, and respiratory rate in a dose-dependent fashion. D-Phe4, Met5-ENK, an analog with behavioral activity but without analgesic or in vitro opiate effects was inactive. Leu5-ENK was studied in detail; typically, heart rate and systemic pressure increased within 20 sec and returned to baseline in less than 180 sec. Intra-arterial injections produced a smaller increase in heart rate than did intravenous injections, but similar increases in systemic arterial blood pressure were recorded. These cardiovascular responses suggest that systemically injected enkephalins suppress baroreceptor reflexes and may have a role in cardiopulmonary regulation.