α_1D-adrenoceptor-induced relaxation on rat carotid artery is impaired during the endothelial dysfunction evoked in the early stages of hyperhomocysteinemia

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• 作者：Claudia Roberta de Andrade ; Sandra Yasuyo Fukada ; Vania Claudia Olivon ; Marcio A.F. de Godoy ; Renato Haddad ; Marcos Nogueira Eberlin ; Fernando Queiroz Cunha ; Heraldo Possolo de Souza ; Francisco R.M. L
• 关键词：Hyperhomocysteinemia ; Carotid artery ; α ; _1D-adrenoceptor ; Modulation ; Relaxation ; Phenylephrine ; Nitric oxide ; Oxidative stress
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：14 August 2006
• 卷：543
• 期：1-3
• 页码：83-91
• 文件大小：425 K

摘要

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 α_1D-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 (α_1A-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 α_1D-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 α_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 α_1D-adrenoceptors by reducing NO biodisponibility.