Cardiovascular responses to cocaine are initially mediated by the central nervous system in rats.
Cocaine produces a pressor response reportedly resulting from both potentiation of peripheral catecholamine activity and a centrally mediated sympathoexcitation. In the present study we sought to differentiate the central nervous system and peripheral contributions to the hemodynamic effects of cocaine. In conscious rats, cocaine (5 mg/kg i.v.) produced a pressor response with two distinct components consisting of a brief, substantial increase in mean arterial pressure (MAP) associated with hindquarters and mesenteric vasoconstriction followed by a sustained, modest response associated with mesenteric vasoconstriction and bradycardia. Pentolinium (7.5 mg/kg i.v.) or adrenal demedullation attenuated the peak increase in MAP by attenuating increases in mesenteric and hindquarters vascular resistance, but did not affect the sustained increase in MAP. Methyl atropine (0.5 or 1 mg/kg i.v.) pretreatment reduced the cocaine-induced increase in systemic vascular resistance and enhanced the hindquarters vasodilation during the sustained MAP response. In contrast, adrenal demedullation abolished the hindquarters vasodilation. The bradycardic response was prevented by pentolinium and reduced by methyl atropine. Sympathetic nerve activity was reduced dramatically after cocaine or procaine administration for several minutes in conscious and in chloralose-anesthetized rats. In several anesthetized rats, the sympathoinhibition was preceded by a brief (3-8 sec) increase in renal sympathetic nerve activity. Procaine or cocaine produced little change in cortical cerebral blood flow as estimated by using a laser Doppler flowmeter. These data suggest that cocaine produces an initial, brief centrally mediated sympathoexcitation, but the sustained, modest pressor response is dependent upon peripheral actions that are diminished by baroreflex activation.
Knuepfer
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MM
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri.
Branch
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D000313:Adrenal Medulla / Q000601:surgery; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure; D002490:Central Nervous System / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002698:Chloralose; D003042:Cocaine / Q000494:pharmacology*; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects
D002698:Chloralose; D001285:Atropine; D003042:Cocaine