Effect of acute intravenous cocaine administration on endothelium-dependent vasodepressor responses to acetylcholine.

Abstract

Cardiovascular events commonly associated with acute and chronic cocaine abuse include coronary vasospasm, arrhythmias, myocardial infarction, and sudden death. It has been suggested that cocaine causes endothelial dysfunction and vasoconstriction by inhibiting local production of nitric oxide and that endothelial dysfunction may be involved in the cardiovascular events associated with cocaine use. The present study investigated the effect of acute intravenous cocaine administration on endothelium-dependent vasodepressor responses to acetylcholine in the anesthetized rat. Rats were anesthetized with intraperitoneally Inactin (140 mg/kg) and catheters were inserted into the jugular vein and iliac artery for the injection of drugs and measurement of systemic arterial pressure. A thermistor catheter was advanced to the aortic arch for the measurement of cardiac output via the thermal dilution technique. A 5 mg/kg intravenous dose of cocaine, which enhances the vasopressor response to norepinephrine and blocks the vasopressor response to tyramine, had no effect on the vasodepressor response to the endothelium-dependent vasodilator acetylcholine. In addition, responses to the nitric oxide-donor sodium nitroprusside and the vasoconstrictor peptide angiotensin II were not altered by administration of cocaine. Acute administration of cocaine in a dose that blocks norepinephrine uptake into adrenergic terminals had no effect on endothelial function as measured by the absence of an effect on the vasodepressor response to intravenous injections of acetylcholine. Although chronic cocaine exposure has been shown to cause vascular dysfunction, eventually leading to impairment of the nitric oxide pathway, it appears that acute cocaine administration does not inhibit this pathway in the anesthetized rat.