Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein

The postjunctional alpha (2)-adrenoceptor-mediated contractility was charac terized in human saphenous vein derived from coronary artery bypass graft s urgery. Human saphenous vein contracted to alpha (2)-adrenoceptor selective agonists BHT-920 (5,6,7,8-Tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azep in-2-amine dihydrochloride; pD(2) = 6.7 +/- 0.1) and UK 14,304 (5-Bromo-6-( 2-imidazolin-2-ylamino)quinoxaline; pD(2) = 7.2 +/- 0.1). BHT-920-induced c ontractions were inhibited by the alpha (2)-adrenoceptor antagonist yohimbi ne (17-Hydroxy-yohimban-16-carboxylic acid methyl ester hydrochloride; pA(2 ) = 8.7 +/- 0.5), but not by the alpha (1)-adrenoceptor antagonist prazosin (1-[4-Amino-6,7-dimethoxy-2-quinazolinyl]-4-[2-furanylcarbonyl]-piperazine hydrochloride; 300 nM). In contrast, prazosin (pK(b) = 7.9 +/- 0.2) potent ly antagonized contractions elicited by the alpha (1)-adrenoceptor agonist phenylephrine ((R)-3-Hydroxy-alpha-[(methylamino)methyl] benzenemethanol hy drochloride; pD(2) = 4.9 +/- 0.1), indicating that both alpha (2)- and alph a (1)-adrenoceptor evoke human saphenous vein contractions. Functional anta gonist activity estimates (pA(2) or pK(b)) obtained for the alpha -adrenoce ptor antagonists ARC 239 (2-[2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl]-4, 4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride), WE 4101 (2-(2,6-D imethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) and HV 723 (alpha -ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy) ethyl)amino )propyl)benzeneacetonitrile) against BHT-920-induced human saphenous vein c ontractions were 7.0 +/- 0.6, 8.3 +/- 0.6 and 7.7 +/- 0.3, respectively. Th e alpha (2)-adrenoceptor subtype affinities (pK(i)) obtained in recombinant human alpha (2A)-, alpha (2B)- and alpha (2C)-adrenoceptor competition bin ding assays were 8.6, 8.3 and 8.6 for yohimbine; 6.3, 8.4 and 7.0 for ARC 2 39; 8.4, 7.5 and 8.4 for WB 4101 and 7.5, 7.4 and 7.9 for HV 723, respectiv ely. Taken together, the binding and functional antagonist activity estimat es obtained in these investigations indicate that alpha (2C)-adrenoceptor i s the predominant postjunctional alpha (2)-adrenoceptor subtype in human sa phenous vein. (C) 2001 published by Elsevier Science B.V.