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Effect of binge cocaine treatment on hindlimb vascular function
Author(s) -
Pradhan Leena,
Dabisch Paul A.,
Liles John T.,
Murthy S. N.,
Baber Syed R.,
Simpson Scott A.,
Agrawal Krishna C.,
Kadowitz Philip J.
Publication year - 2005
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1083
Subject(s) - medicine , phenylephrine , endocrinology , vasodilation , norepinephrine , vasoconstriction , endothelium , sodium nitroprusside , hindlimb , anesthesia , blood pressure , nitric oxide , dopamine
Chronic cocaine abuse is known to cause endothelial dysfunction and atherosclerosis. The present study investigated the effect of binge cocaine treatment, a model for chronic cocaine abuse, on the blood ßow responses to the adrenergic agonists norepinephrine, phenylephrine and isoproterenol, the endothelium‐dependent vasodilator acetylcholine, and the endothelium independent vasodilator sodium nitroprusside (SNP) in the hindlimb vascular bed of male Sprague Dawley rats. Rats received either single binge or double binge treatment. Each binge treatment consisted of three doses of cocaine (30 mg kg −1 i.p.) for 3 days. For double binge treatment, there was a 4 day recovery period between the binges. At the end of the treatment the rats were anesthetized and agonists were administered into the right hindlimb circulation through a catheter in the left iliac artery and blood ßow responses were measured with a ßow probe around the right iliac artery. Rats receiving double cocaine binges showed a significant decrease in the magnitude and duration of the blood ßow response to norepinephrine and a decrease in the duration of the blood ßow response to phenylephrine, isoproterenol and acetylcholine when compared with saline controls. The blood ßow response to SNP was not changed. Total plasma nitrate‐nitrite levels were significantly reduced and big endothelin levels were significantly increased in rats receiving double cocaine binges. This study demonstrates that binge cocaine treatment can alter endothelial function, while not changing smooth muscle function, and impairs the adrenergic pathway. Copyright © 2005 John Wiley & Sons, Ltd.