Cardiorespiratory responses to D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin after administration into the fourth cerebral ventricle of the rat: interaction with cholinergic mechanisms.

The purpose of this study was to investigate the effect of the synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin (FK 33-824), on blood pressure, heart rate, respiratory rate and survival, after its injection into the 4th cerebral ventricle of Wistar rats. The animals were either anesthetized with pentobarbital and breathing spontaneously or unanesthetized. The unanesthetized rats were previously instrumented with cannulas in the 4th cerebral ventrical and a systemic artery. In anesthetized rats, intracerebroventricular administration of FK 33-824 produced a transient increase in blood pressure followed by sustained hypotension, bradycardia and respiratory depression in a dose-dependent manner. Fatalities were observed over a 150-min observation period and were a function of dose. Pretreatment with atropine sulfate (1 mg/kg i.v.) produced an accentuated response with greater hypotension, bradycardia and shorter survival. In another group of anesthetized rats, in which hypoventilation was prevented by mechanical ventilation, blood pressure and heart rate were not as reduced as in spontaneously breathing rats. Hypotension, bradycardia and hypoventilation were less marked in unanesthetized rats, compared to anesthetized rats. Thus, FK 33-824 in the 4th cerebral ventricle of the rat produces marked changes in blood pressure in anesthetized as well as unanesthetized animals, but these changes were less in the unanesthetized or mechanically ventilated animal and greater after atropine, suggesting that these effects are mediated by respiratory depression and are antagonized by the cholinergic nervous system.