Effects of cocaine on adrenal sympathetic nerve discharge in anesthetized rats.
Cocaine increases the circulating levels of plasma catecholamines, presumably via the activation of the sympathoadrenal axis. However, a number of reports have shown that the predominant response to cocaine is a generalized decrease in sympathetic nerve activity. One possible explanation for the increase in plasma catecholamines may be that the adrenal sympathetic nerve is less sensitive to the sympathoinhibitory actions of cocaine than are other nerves. This study compared the effects of cocaine on adrenal and renal sympathetic nerve discharge (SND) recorded simultaneously in pentobarbital-anesthetized rats. Cocaine produced dose-related decreases in both renal and adrenal SND; however, the decreases in adrenal SND were significantly smaller than in renal SND. Cocaine also elicited pressor responses in these rats. The decreases in adrenal SND were similar in baroreceptor intact and sinoaortically denervated rats, indicating that pressor-mediated baroreceptor reflex activation was not responsible for the decrease in adrenal SND. In a separate group of rats, i.v. administration of desipramine decreased both adrenal and renal SND. As with cocaine, the decreases in adrenal SND after desipramine were smaller, suggesting that the differences in the neural responses did not reflect a differential local anesthetic effect of cocaine on the two nerves. In conclusion, these studies showed that cocaine decreases adrenal SND in pentobarbital-anesthetized rats. However, the adrenal sympathetic nerve is less sensitive than the renal nerve to the sympathoinhibitory actions of cocaine. Whether the adrenal SND remaining after cocaine contributes to the increase in plasma catecholamines produced by this drug remains to be determined.
Abrahams
T P
TP
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112, USA.
Varner
K J
KJ
D000311:Adrenal Glands / Q000187:drug effects / Q000294:innervation*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D009294:Narcotics; D003042:Cocaine; D003891:Desipramine