α1d-adrenoceptor-induced Relaxation On Rat Carotid Artery Is Impaired During The Endothelial Dysfunction Evoked In The Early Stages Of Hyperhomocysteinemia

Hyperhomocysteinemia is a known risk factor for cardiovascular diseases, but the underlying mechanisms of this pathology are complex. We aimed to evaluate the effect of hyperhomocysteinemia in vasorelaxations induced by α1D-adrenoceptor agonists. Vascular reactivity of rat carotid artery to the α-adrenoceptor agonist, phenylephrine, was enhanced in hyperhomocysteinemia. Mechanical removal of endothelium did not modify the carotid responsiveness to phenylephrine, compared to control. Phenylephrine induces endothelium-dependent relaxation, in the presence of 5-methyl urapidil (α1A-adrenoceptor antagonist). We hypothesised that endothelial-relaxant α1-adrenoceptors are impaired by hyperhomocysteinemia. Incubation with prazosin (selective α1-adrenoceptor antagonist) or BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7, 9-dione dihydrochloride) (selective α1D-adrenoceptor antagonist), similarly inhibited phenylephrine-induced relaxations in both control and hyperhomocysteinemic carotids. Immunohistochemistry showed enhanced immunoreactivity for eNOS and iNOS in hyperhomocysteinemic rats. In carotid arteries from hyperhomocysteinemic rats there was a decrease in superoxide dismutase activity and enhanced superoxide anion production. We conclude that α1D-adrenoceptors mediate endothelium-dependent relaxation triggered by phenylephrine in rat carotid artery and affect the final tone. Furthermore, the enhanced phenylephrine-induced contraction in carotid artery due to hyperhomocysteinemia is endothelium-dependent and involves a loss of the inhibitory effect of relaxant α1D-adrenoceptors by reducing NO biodisponibility. © 2006 Elsevier B.V. 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