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Type: Artigo de periódico
Title: alpha(1D)-adrenoceptor-induced relaxation on rat carotid artery is impaired during the endothelial dysfunction evoked in the early stages of hyperhomocysteinemia
Author: de Andrade, CR
Fukada, SY
Olivon, VC
de Godoy, MAF
Haddad, R
Eberlin, MN
Cunha, FQ
de Souza, HP
Laurindo, FRM
de Oliveira, AM
Abstract: 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 alpha(1D)-adrenoceptor agonists. Vascular reactivity of rat carotid artery to the a-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 (alpha(1A)-adrenoceptor antagonist). We hypothesised that endothelial-relaxant alpha(1)-adrenoceptors are impaired by hyperhomocysteinemia. Incubation with prazosin (selective alpha(1)-adrenoceptor antagonist) or BMY7378 (8-[2-[4-(2-methoxyphenyl)-l-piperazinyl]ethyl]-8-azaspiro [4,5]decane-7, 9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist), similarly inhibited phenylephrine-induced relaxations in both control and hyperhomocysteinemic carotids. Immumohistochemistry showed enhanced immunoreactivity for eNOS and NOS 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 alpha(1D)-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 alpha(1D)-adrenoceptors by reducing NO biodisponibility. (c) 2006 Elsevier B.V. All rights reserved.
Subject: hyperhomocysteinemia
carotid artery
nitric oxide
oxidative stress
Country: Holanda
Editor: Elsevier Science Bv
Rights: fechado
Identifier DOI: 10.1016/j.ejphar.2006.06.003
Date Issue: 2006
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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