D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin in the nucleus tractus solitarius of the rat produces cardiorespiratory depression.

1. The synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin (FK 33-824). 1 or 2 micrograms, after its injection into the nucleus tractus solitarius (NTS) of Wistar rats, anesthetized with pentobarbital and breathing spontaneously, produced a transient increase in blood pressure followed by sustained and significant (P less than 0.05) hypotension and bradycardia. This occurred in a dose dependent manner. 2. FK 33-824 in the NTS, 1 or 2 micrograms, also produced a marked respiratory depression. 3. In anesthetized rats, in which hypoventilation was prevented by mechanical ventilation, there was a definite reduction in blood pressure and heart rate that was considerably and significantly (P less than 0.05) less than that observed in spontaneously breathing rats. 4. Blood pressure fluctuations occurred after NTS injection that were more marked in spontaneously breathing animals but still occurred in animals that were ventilated mechanically. 5. FK 33-824, 1 and 2 micrograms in the NTS was fatal within 100 min for all animals but was prevented by mechanical ventilation. Higher doses of FK 33-824, 10 micrograms in the NTS, however, induced fatal ventricular arrhythmias even in the mechanically ventilated rat. 6. Thus, FK 33-824 in the NTS decreases blood pressure and heat rate in spontaneously breathing as well as mechanically ventilated rats, but much of the effect on blood pressure and heart rate is due to the profound respiratory depression in the spontaneously breathing rat.