%0 Journal Article
%T Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries
%A Elise R Hedegaard
%A Edgaras Stankevicius
%A Ulf Simonsen
%A Ole Fr£¿bert
%J BMC Physiology
%D 2011
%I BioMed Central
%R 10.1186/1472-6793-11-8
%X In prostaglandin F2¦Á (PGF2¦Á, 10 ¦ÌM)-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 ¦ÌM) markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2¦Á-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 ¦ÌM, NG-nitro-L-Arginine) reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride)(10 ¦ÌM) inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 ¦ÌM) and the putative NADPH oxidase inhibitor apocynin (10 ¦ÌM) leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene glycol) catalase (300 u/ml) inhibited H2O2 vasodilation, but failed to affect vasodilation to O2 lowering. Neither did PEG-SOD (polyethylene glycol superoxide dismutase)(70 u/ml) affect vasodilation to O2 lowering. The mitochondrial inhibitors rotenone (1 ¦ÌM) and antimycin A (1 ¦ÌM) both inhibited hypoxic vasodilatation.The present results in porcine coronary arteries suggest NO contributes to hypoxic vasodilation, probably through K channel opening, which is reversed by addition of ET-1 and enhanced by endothelin receptor antagonism. These latter findings suggest that endothelin receptor activation counteracts hypoxic vasodilation.The systemic vascular re
%U http://www.biomedcentral.com/1472-6793/11/8