Role of Nitric Oxide in Cocaine-Induced Acute Hypertension

Abstract

Cocaine causes acute hypertension by blocking catecholamine reuptake. There is evidence that it also impairs the peripheral endothelial nitric oxide system, which is normally vasodilatory. We further explored the role of nitric oxide in cocaine-induced vasoconstriction in anesthetized rats, and in vitro by using isolated carotid artery segments. Cocaine administered intravenously in rats increased mean arterial pressure by 30 to 40 mm Hg within 1 min. This effect was dose dependent and the maximum effect was observed at a dose of 1.25 mg/kg. The prototype catecholamine norepinephrine induced a similar increase in blood pressure. When rats were pretreated with NG-monomethyl-L-arginine (L-NMMA, a blocker of nitric oxide) and challenged with cocaine, the increase in blood pressure was blocked by 80%, whereas pretreatment with L-NMMA did not block norepinephrine-induced vasoconstriction. Both cocaine and norepinephrine also induced an immediate vasoconstriction in isolated carotid artery preparations. The in vitro vasoconstriction induced by cocaine was blocked by pretreatment with L-NMMA, whereas L-NMMA did not block the norepinephrine-induced vasoconstriction in vitro. Furthermore, carotid artery stripped of endothelium responded to norepinephrine but failed to respond to L-NMMA or cocaine. S-nitroso-N-acetyl-D,L-penicillamine (SNAP)-a precursor of nitric oxide- stimulated nitric oxide production in control coronary artery fragments. When these fragments were incubated with cocaine there was a 20% reduction in the production of nitrite oxide. These results suggest that cocaine exerts its peripheral vasoconstriction at least in part by inhibiting local vasodilator nitric oxide.

Management of Cocaine-Associated Chest Pain and Myocardial Infarction

“…20 In addition to ␣-adrenergic stimulation, cocaine has been shown to increase levels of endothelin-1, which is a powerful vasoconstrictor, 21 and to decrease production of nitric oxide, which is a vasodilator. 22 Thus, cocaine decreases oxygen supply and induces myocardial ischemia through a variety of mechanisms.…”

Spontaneous Coronary Artery Dissection and Implantation of Absorb Bioresorbable Drug-Eluting Stent in Cocaine-Related Acute Coronary Syndrome

“…Cocaine-induced vasoconstriction is often secondary to the block of the reuptake of noradrenaline and dopamine with a powerful sympathetic response due to sustained alpha-and beta-adrenergic stimulation. In addition, cocaine has been shown to increase levels of endothelin-1 [15] and to decrease production of nitric oxide [16]. Cocaine may enhance platelet activation with potential intra-coronary thrombosis [17].…”

Rabdomiólisis e insuficiencia renal aguda por consumo de cocaína: caso clínico

“…En ratas tratadas con un inhibidor de la NO sintasa, se ha demostrado 80% de reducción en la respuesta presora, al exponerlas a la acción de la cocaína 17 . Las células endoteliales producen enzima convertidora de angiotensina en forma endógena, sugiriendo que el efecto de los IEca en la presión arterial y función cardiovascular puede ser debido a efectos locales en las células endoteliales 16 . El captopril regula negativamente la liberación de ET-1 en cultivos de células endoteliales 17 ; en un experimento en que ratas fueron expuestas a niveles letales de cocaína, el uso de captopril y diazepam, incrementó el tiempo de sobrevida 18 .…”