Sensitization of Arteries, Veins, and Small Vessels to Norepinephrine After Cocaine

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Abstract
The effects of cocaine on the responses of arteries, veins, and small vessels to norepinephrine were studied. Intra-arterial norepinephrine was injected or infused into perfused forelegs of dogs. Angiotensin and serotonin were used as agonists. The effects of postganglionic sympathetic stimulation and of intra-arterial tyramine were tested also. Cocaine in doses of 0.5, 5.0, and 10 mg/kg IV sensitized the arterial and venous segments to norepinephrine; the responses of small vessels were not augmented significantly. The effects of angiotensin and serotonin were not increased. The vasoconstrictor effect of weak and strong submaximal postganglionic sympathetic nerve stimulations was reduced and that of intra-arterial tyramine was suppressed after cocaine. The results allow us to conclude that vascular supersensitivity to norepinephrine after cocaine is not a uniform phenomenon but it is restricted to certain vascular segments. The reason for the sensitization of arteries and veins but not small vessels is unknown. The observations are discussed in light of the recent hypothesis proposed by Furchgott et al on the mechanism of action of cocaine.