Microvascular effects of cocaine; interaction with nitrendipine and enalaprilat.
Cocaine abuse can cause cardiovascular damage leading to hypertension, myocardial ischaemia and infarction. This might be partly due to the effects of cocaine on the microcirculation about which little is known, although its effects on the macrovessels are well documented. Accordingly, we used in vivo videomicroscopy to study the vasoconstrictive effect of cocaine on arterioles of different diameter. They were classified into three orders (A2, A3, A4) according to their position in the microvascular network and their diameter. Since calcium antagonists have been reported to exert a protective effect against the cardiovascular disorders induced by cocaine, we tested the hypothesis that this protective action occurs in the microcirculation. We found that intra-arterial administration of the calcium antagonist Nitrendipine greatly inhibited the vasoconstriction induced by cocaine in all three arteriole orders. The degree of inhibition ranged from 44 to 56%. Combined administration of benzodiazepine and an angiotensin converting enzyme inhibitor has also been reported to protect rats against cocaine-induced hypertension and to increase survival rates after a toxic dose of cocaine. Since the mechanisms of this protection are not yet clear, we also studied the effect of the angiotensin converting enzyme inhibitor Enalaprilat on cocaine-induced vasoconstriction. Intra-arterial administration of Enalaprilat inhibited this vasoconstriction slightly but significantly in arteriole orders 2 and 3 by 27 and 24% respectively, but not in order 4. We concluded that Nitrendipine is a powerful inhibitor of cocaine-induced vasoconstriction in the microcirculation. The small but significant inhibition found with Enalaprilat for the larger arterioles suggests that the local angiotensin II level may affect the response to cocaine. However, since the Enalaprilat-induced inhibition was very limited, we conclude that mechanisms other than those occurring in the peripheral microcirculation account for the protection afforded by Enalaprilat against the harmful effects of cocaine.
Vicaut
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Institut National de la Santé et de la Recherche Medicale., Hopital F. Widal, Paris, France.
Trouvé
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Hou
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004347:Drug Interactions; D015773:Enalaprilat / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D009568:Nitrendipine; D015773:Enalaprilat; D003042:Cocaine