EFFECTS OF ANTIDOTES TO COCAINE ON THE DEREGULATION OF THE BAROREFLEXBY THE ALKALOID

Cocaine exerts in the rat an inhibitory effect on the baroreflex induc ed by bilateral clamping of the carotid arteries. The present series o f experiments were designed to test the effectiveness of cocaine antid otes on this deregulation of the baroreflex. Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal ar tery, and their carotid arteries were exposed. The pressure signal fro m the caudal artery was treated on line by a microcomputer for continu ous display of blood pressure and heart rate measurements, The animals were administered intraperitoneally either 50 mg cocaine or an equal volume of saline, Five minutes later, they were administered either sa line or proven antidotes to cocaine (diltiazem, nicardipine, enzyme co nverting inhibitor [ECI], enalaprilat associated with diazepam). After 2 min, stimulation of the baroreceptor was performed by bilateral cla mping of the two carotids for a period of 2 min. The measures of the m aximal variation in systolic pressure before and after clamping indica ted a significant difference between saline and cocaine treated animal s (P < 0.05), with the former displaying a much greater increment in b lood pressure after clamping. The cocaine-treated animals, administere d diltiazem, nicardipine, and ECI associated with diazepam, presented after damping of the carotid arteries a normal baroreflex with increme nts in blood pressure no significantly different from those occurring in the animals receiving saline, but significantly different from thos e administered cocaine only (P < 0.05). Baroreflex deregulation by coc aine may also be restored by an angiotensin II receptor antagonist, Th e possible role of this peptide in mediating in part baroreflex activi ty is discussed.