Central cardiovascular effects of narcotic analgesics and enkephalins in rats

1. The cardiovascular effects of morphine, fentanyl, [D-Ala2]-met-enkephalinamide were analyzed after intracisternal injection in anaesthetized rats. PaO2 was measured as an index of respiratory function. 2. At low doses in spontaneously breathing rats, morphine, fentanyl and [D-Ala2]-met-enkephalinamide induced a pressor response with slight tachycardia and no significant change in PaO2. 3. The pressor response appeared to be due to activation of opiate receptors and mediated through the sympathetic nervous system. 4. High doses of morphine and [D-Ala2]-met-enkephalinamide induced a biphasic effect with a secondary hypotension associated with bradycardia in spontaneously breathing rats. A marked reduction in PaO2 was found during the depressor phase. 5. High doses of [D-Ala2]-met-enkephalinamide produced only a pressor response in artificially-ventilated rats with no signs of secondary hypotension. 6. Our data support the idea that morphinomimetic agents are centrally pressor at low doses in the rat. The respiratory depression observed with high doses may be the cause of hypotension.