Adrenergic mechanisms underlying cardiac and vascular responses to cocaine in conscious rats.
The contribution of adrenergic receptors to the cardiovascular responses to cocaine (5 mg/kg i.v.) were examined in conscious, free-moving rats instrumented for continuous measurement of arterial pressure, heart rate and blood flows in the mesentery and hindquarters or ascending aorta. Cocaine elicits an immediate (peak) and sustained pressor response with a concomitant reduction in heart rate. Prazosin (0.1 mg/kg i.v.) pretreatment significantly reduced both the peak and sustained pressor responses by attenuating the increases in systemic, mesenteric and hindquarters vascular resistances. Idazoxan pretreatment (1 mg/kg i.v.) attenuated the peak increase in hindquarters vascular resistance. Whereas propranolol pretreatment (1 mg/kg i.v.) attenuated the peak pressor response, the sustained pressor response was enhanced due to increased hindquarters and systemic vascular resistances. Metoprolol pretreatment (1 mg/kg i.v.) enhanced the sustained pressor response to cocaine, in part due to increased heart rate and mesenteric vascular resistances. Upon examination of the cardiac effects of cocaine, a sustained bradycardic response was observed, whereas stroke volume and cardiac output were relatively unaffected. The bradycardic response to cocaine was attenuated by yohimbine (0.1 mg/kg i.v.), prevented by prazosin and converted to a tachycardia after idazoxan (1 mg/kg) pretreatment. After propranolol pretreatment, cocaine substantially decreased cardiac output and stroke volume. Our results demonstrate that cocaine produces a biphasic pressor response in conscious rats and that the mechanisms underlying the dual responses vary in intensity and mode of action in different vascular beds, but are primarily dependent upon alpha-1 adrenergic receptor-mediated vasoconstriction.
Department of Pathology, St. Louis University School of Medicine, Missouri.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology* / Q000633:toxicity; D004146:Dioxanes / Q000494:pharmacology; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D019329:Idazoxan; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D015016:Yohimbine; D011433:Propranolol; D008790:Metoprolol; D003042:Cocaine; D011224:Prazosin; D019329:Idazoxan