Effect of binge cocaine treatment on hindlimb vascular function

• Published in: Journal of applied toxicology 2005-11, Vol.25 (6), p.479-490
• Main Authors: Pradhan, Leena, Dabisch, Paul A., Liles, John T., Murthy, S. N., Baber, Syed R., Simpson, Scott A., Agrawal, Krishna C., Kadowitz, Philip J.
• Format: Article
• Language: English
• Subjects: Acetylcholine; adrenergic; Animals; binge; Biological and medical sciences; Bradykinin; cocaine; Cocaine - administration & dosage; Cocaine - toxicity; Cocaine-Related Disorders - blood; Cocaine-Related Disorders - physiopathology; Disease Models, Animal; Dose-Response Relationship, Drug; Drug addictions; endothelin; Endothelin-1 - blood; Endothelium, Vascular - drug effects; Hindlimb - blood supply; Hindlimb - physiopathology; Male; Medical sciences; nitric oxide; Nitroprusside; Rats; Rats, Sprague-Dawley; Regional Blood Flow - drug effects; Time Factors; Toxicology; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1083

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.