Effects of antidotes to cocaine on the deregulation of the baroreflex by the alkaloid.
Cocaine exerts in the rat an inhibitory effect on the baroreflex induced by bilateral clamping of the carotid arteries. The present series of experiments were designed to test the effectiveness of cocaine antidotes on this deregulation of the baroreflex. Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery, and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous 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 saline or proven antidotes to cocaine (diltiazem, nicardipine, enzyme converting inhibitor [ECI], enalaprilat associated with diazepam). After 2 min, stimulation of the baroreceptor was performed by bilateral clamping of the two carotids for a period of 2 min. The measures of the maximal variation in systolic pressure before and after clamping indicated a significant difference between saline and cocaine treated animals (P < 0.05), with the former displaying a much greater increment in blood pressure after clamping. The cocaine-treated animals, administered diltiazem, nicardipine, and ECI associated with diazepam, presented after clamping of the carotid arteries a normal baroreflex with increments in blood pressure not significantly different from those occurring in the animals receiving saline, but significantly different from those administered cocaine only (P < 0.05). Baroreflex deregulation by cocaine may also be restored by an angiotensin II receptor antagonist. The possible role of this peptide in mediating in part baroreflex activity is discussed.
Trouvé
R
R
Hopital Fernand Widal, Paris, France.
Nahas
G G
GG
Arnaoudov
P I
PI
Latour
C
C
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000931:Antidotes; D009529:Nicardipine; D004110:Diltiazem; D015773:Enalaprilat; D003042:Cocaine