Cardiorespiratory effects of D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin in the third ventricle, and in anterior hypothalamic and paraventricular areas of the rat brain.
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.
Rabkin
S W
SW
Department of Medicine, University of British Columbia, Vancouver, Canada.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000401:mortality; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects*; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007032:Hypothalamus, Anterior / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D012121:Respiration, Artificial
D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin