INTRINSIC CARDIAC ENKEPHALINS AND VAGAL CONTROL

Met-enkephalin-arg-phe (MEAP) has been identified in acid extracts of canine heart. The effects of synthetic MEAP on the vagal control of he art rate and atrial contractility were investigated in anesthetized do gs. Arterial MEAP (3 nmol/min/kg) inhibited right vagal bradycardia by two thirds. Postinfusion responsiveness to vagal stimulation returned to normal with an estimated half-time of 2-3 min. Inhibition by MEAP was reversed by the high affinity opiate antagonist, diprenorphine at pmolar concentrations. Since MEAP did not alter the negative chronotro pic effect of methacholine, the effective site must reside in the effe rent vagal tract proximal to nodal muscarinic receptors. Left vagal st imulation dramatically suppresses left atrial contractile activity. In fused MEAP also interrupts this negative inotropic response through a diprenorphine sensitive mechanism Increasing MEAP infusions (0.09 - 3. 00 nmol/min/kg) produced a graded suppression of vagal bradycardia wit h an ED50 near 0.3 nmol/min/kg. Heart rate dose responses for methioni ne-enkephalin were shifted to the right of MEAP and required approxima tely 3 X the dose to produce the same effect. The data suggest that th e intrinsic cardiac enkephalin, MEAP can regulate vagal control of hea rt rate at physiologically achievable concentrations and may serve as a local regulator of the parasympathetic/myocardial interface.