Cocaine inhibits baroreflex control of blood pressure by actions at arterial baroreceptors.
Blood pressure and heart rate often increase during cocaine intoxication, but the mechanisms of these cardiovascular responses are poorly understood. The most often suggested theories are central nervous system mechanisms involving the blockade of neuronal transmitter uptake. Cocaine also has potent local anesthetic properties, and in this study we tested the possible role of peripheral actions of cocaine at baroreceptor afferents. Single fiber baroreceptors were recorded using an in vitro preparation of the rat aortic arch. Diameter, pressure, and baroreceptor discharge were recorded. Cocaine perfused through the lumen of the aortic arch at a suprathreshold pressure reduced baroreceptor discharge within 90 s of entering the lumen of the aorta. Slow ramps of pressure elicited complete pressure- and diameter-discharge curves every 5 min. Beginning at about 1 microM, cocaine inhibited baroreceptor function; threshold increased, the maximum discharge decreased, and at 100 microM cocaine, all discharge ceased. The vasodilator nitroprusside or the alpha 1-adrenoreceptor antagonist prazosin did not affect baroreceptor responses to cocaine. In in vivo tests in rabbits, cocaine that perfused through a vascularly isolated carotid sinus reduced the slope of the baroreflex relationship between carotid sinus pressure and systemic mean arterial pressure. Significant depression of baroreceptor function was found at concentrations similar to the plasma cocaine levels measured in clinical studies. The local anesthetic properties of cocaine may be involved in baroreceptor effects. Our studies suggest a possible contributing role of a new site of action of cocaine outside the central nervous system. Compromise of baroreceptor reflexes could facilitate the development of serious cardiovascular complications associated with cocaine abuse.
Andresen
M C
MC
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
Yang
M
M
Nelson
S H
SH
Steinsland
O S
OS
D000818:Animals; D001158:Arteries / Q000502:physiology*; D001794:Blood Pressure; D002346:Carotid Sinus / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009599:Nitroprusside / Q000494:pharmacology; D009994:Osmolar Concentration; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects / Q000502:physiology
D009599:Nitroprusside; D003042:Cocaine; D011224:Prazosin