d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Arrhythmias--Cardiac

The purpose of this study was to investigate the cardiorespiratory effects of the synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin (FK 33-824) after its administration into the anterior hypothalamic area, paraventricular hypothalamic nuclei and third ventricle. Wistar rats, anaesthetised with pentobarbitone and breathing spontaneously, received an injection of FK 33-824, 1 or 2 micrograms into one of these three areas. FK 33-824 produced significant (analysis of variance, p less than 0.05) and sustained hypotension of similar degree following injection into any one of these three sites. Significant (p less than 0.05) reductions in heart rate and respiratory rate were also observed. Hypotension and bradycardia occurred, but to a lesser degree, when respiratory depression was prevented by mechanical ventilation. FK 33-824 produced fatal bradyarrhythmias in spontaneously breathing and mechanically ventilated animals. When respiratory depression was prevented by mechanical ventilation, survival was lowest after third ventricular administration followed by paraventricular and anterior hypothalamic injections. Thus D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin produced marked vasodepression and respiratory depression in the rat. These effects were interrelated but reductions in heart rate and blood pressure also occurred independently of the respiratory depression.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cerebral Ventricles; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dose-Response Relationship, Drug; Heart Rate; Hypothalamus, Anterior; Male; Rats; Rats, Inbred Strains; Respiration; Respiration, Artificial

The cardiovascular effects of D-Ala-2-Me-Phe-4-Met-(0)-Ol enkephalin were investigated after its administration into the fourth cerebroventricle of the guinea pig. This enkephalin is a synthetic Met-enkephalin analog that is more resistant to degradation and has a high affinity for opioid receptors. It produced a significant increase in blood pressure and decline in heart rate. At high concentrations, 100 micrograms/kg plus 100 micrograms/kg/hr in the fourth ventricle, it produced bradyarrhythmias that were sometimes fatal. At doses that did not alter survival or produce arrhythmia, namely 30 micrograms/kg plus 25 micrograms/kg/hr in the fourth ventricle, the response to digitalis was assessed. Significant leftward shifts in the relationships between digoxin and arrhythmia occurrence and development of fatal arrhythmias were observed. Thus, D-Ala-2-Me-Phe-4-Met-(0)-Ol enkephalin has definite cardiovascular effects that include potentiation of digoxin arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Digoxin; Guinea Pigs; Heart Rate; Injections, Intraventricular; Male