Effects of intravenously administered Leu- or Met-enkephalin on arterial blood pressure

The purpose of these studies was to determine if two endogenous opioids, leucine (Leu) and methionine (Met) -enkephalin, alter blood pressure and, if so, by what mechanisms. Studies from our laboratory show that intravenous administration of Leu-enkephalin in doses of 0.032-320 microgram/kg induced a biphasic response in pentobarbital-anesthetized cats. A transient rise in mean arterial pressure was followed by a more prolonged decline. Administration of Met-enkephalin caused only a decline in mean arterial pressure. Neither agent significantly altered heart rate, venous pressure or the EKG. Having determined that both enkephalins altered blood pressure and observed that the responses were qualitatively different, selected pharmacological antagonists were employed to see if the alterations in blood pressure could be blocked. Naloxone blocked the hypertensive responses and antagonized the hypotensive effects seen with the administration of Leu-enkephalin. Naloxone also shifted the dose-effect curve of Met-enkephalin to the right. Diphenhydramine attenuated both the hypertensive and hypotensive responses of Leu-enkephalin. However, diphenhydramine pretreatment did not alter the decline in blood pressure seen with the higher doses of Met-enkephalin. Propranolol exerted some antagonistic activity in association with the rise in blood pressure seen with Leu-enkephalin, but propranolol did not alter the drop in pressure observed with the administration of either enkephalin. These results show that intravenous administration of the enkephalins can alter blood pressure and these effects are not alike for each enkephalin. Additionally, the enkephalins are not blocked in the same fashion by antagonists, giving support to the hypothesis that the two enkephalins interact with different receptors.