non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteriesnon-endothelial内皮素抵消低氧在猪冠状动脉大血管舒张.pdfVIP

Hedegaard et al. BMC Physiology 2011, 11:8 /1472-6793/11/8 RESEARCH ARTICLE Open Access Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries 1* 2 1 1,3 Elise R Hedegaard , Edgaras Stankevicius , Ulf Simonsen and Ole Fröbert Abstract Background: The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1) is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO) vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA). We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Results: In prostaglandin F2a (PGF2a, 10 μM)-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 O concentrations except at 1% O . The endothelin receptor antagonist 2 2 SB217242 (10 μM) 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