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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 26, 2005; DOI: 10.1124/jpet.105.087452


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Received for publication April 5, 2005.
Revised May 24, 2005.
Accepted for publication May 24, 2005.

Effects of cocaine on nitric oxide production in bovine coronary artery endothelial cells

Jiale He 1, Shumei Yang 2, Lubo Zhang 3*

1 Loma Linda University 2 California State University San Bernardino 3 Loma Linda University School of Medicine

* Address correspondence to: E-mail: lzhang{at}som.llu.edu

Abstract

Cocaine decreases coronary artery endothelial-dependent vasorelaxation. To explore the potential mechanisms, the present study examined the effect of cocaine on nitric oxide release in bovine coronary artery endothelial cells (BCAECs). In the absence of cocaine, basal nitric oxide release from BCAECs continued to accumulate in the medium over the period from 6 to 72 h. Cocaine significantly decreased nitric oxide release at each time point of the study. At 48 h treatment, cocaine (3 to 30 µM) produced a dose-dependent decrease in nitric oxide release in BCAECs. In accordance with its inhibition of nitric oxide release, cocaine decreased eNOS protein levels in BCAECs in a dose-dependent manner. In addition to the prolonged effect, cocaine pretreatment for 1 h significantly decreased basal and ATP-induced nitric oxide release in BCAECs. Whereas acute cocaine treatment did not affect basal levels of free intracellular calcium concentrations in BCAECs, it significantly decreased the ATP-induced elevation of intracellular calcium and increased its time lag to reach the peak. A quantitative approach by immunofluorescence microscopy revealed that cocaine significantly increased eNOS localized at the cell membrane in BCAECs. Collectively, the results suggest that cocaine inhibits nitric oxide release in BCAECs by decreasing intracellular calcium mobilization, increasing the inactive state of eNOS, and decreasing eNOS protein levels.


Key words: bovine, calcium, cocaine, coronary, endothelium, nitric oxide


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Postgrad. Med. J.Home page
D. M Wood, D. Hill, A. Gunasekera, S. L Greene, A. L Jones, and P. I Dargan
Is cocaine use recognised as a risk factor for acute coronary syndrome by doctors in the UK?
Postgrad. Med. J., May 1, 2007; 83(979): 325 - 328.
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