Nucleotide-evoked relaxation of human coronary artery

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• 作者：Hansmann ; Georg ; Ihling ; Christian ; Pieske ; Burkert ; Bü ; ltmann ; Ralph
• 关键词：Coronary artery ; Human ; Endothelium ; Vasodilation ; P2 receptor ; Nucleotide ; UTP
• 刊名：European Journal of Pharmacology
• 出版年：1998
• 出版时间：October 16, 1998
• 年：1998
• 卷：359
• 期：1
• 页码：59-67
• 全文大小：396 K

文摘

Endothelium-dependent dilation of coronary blood vessels in response to ATP and related nucleotides has been demonstrated in various animal species. The aim of the present study was to investigate a possible relaxant effect of ATP, the adenine nucleotides 2-methylthio ATP (MeSATP) and adenosine 5′-O-(2-thiodiphosphate) (ADPβS), and the pyrimidine nucleotide UTP in isolated human coronary artery. In endothelium-intact rings of human coronary artery precontracted with K⁺ (20–40 mM), the nucleotides caused relaxation. Average maximal percentage relaxations and average EC₅₀ values (concentrations causing half-maximal relaxation) were 89 % and 47.1 μM for ATP, 28 % and 0.3 μM for MeSATP, 35 % and 0.6 μM for ADPβS, and 49 % and 1.6 μM for UTP. For each of the four agonists, the potency to elicit relaxation varied greatly between individual rings, so that equi-relaxing concentrations spanned several orders of magnitude. Moreover, the sensitivities to ATP and UTP, when tested in the same ring, were not correlated. Mechanical removal of the endothelium as well as N^G-nitro--arginine methyl ester (-NAME; 30 μM), an inhibitor of nitric oxide synthase, abolished the relaxation caused by MeSATP, ADPβS and UTP and greatly attenuated the response to lower concentrations of ATP (3.2–320 μM), but high concentrations of ATP (320 and 1000 μM) caused relaxation also in endothelium-denuded preparations and in the presence of -NAME. High concentrations of ADPβS (32 and 100 μM) and UTP (320 and 1000 μM) caused contraction of endothelium-denuded preparations. Thus, extracellular nucleotides cause endothelium-dependent, primarily nitric oxide-mediated relaxation of human coronary artery. ATP in addition causes endothelium-independent relaxation. The receptors activated by the nucleotides appear to be unevenly distributed on the coronary endothelium.