The purpose of this study was to determine if endothelin-1 (ET-1) mediates endothelium-dependent enhancement of rat aortic contractility following exposure to hypoxia. Rats breathed room air or 10% oxygen for 12 or 48 h. Thoracic aortas and plasma were analysed for ET-1 content by radioimmunassay. Aortic rings were mounted in organ bath myographs for measurement of isometric tension during activation by phenylephrine (10(-9)-10(-4) M), in the presence and absence of BQ-123. In some rings, the endothelium was removed. Plasma ET-1 levels were 0.79+/-0.09 pg/ml, 2.00+/-0.36 and 1.88+/-0.21 pg/ml, in normoxic rats and rats exposed to hypoxia for 12 or 48 h respectively (P<0.001, 12 or 48 h vs. control). Aortic ET-1 concentrations were 202.3+/-20.8 fg/mg in normoxic rats, compared to 274.9+/-40.6 fg/mg and 292.4+/-24.4 fg/mg in rats exposed to hypoxia for 12 and 48 h, respectively (P<0.01, 12 or 48 h vs. control) and 155.0+/-43.1 fg/mg in de-endothelialized aortas from rats exposed to hypoxia for 48 h (P>0.05 vs. normoxic controls). Maximum tension during phenylephrine-induced contraction was 0.46+/-0.04 mg/g and 0.33+/-0.03 mg/g in endothelialized rings from rats exposed to hypoxia for 48 h in the presence and absence of BQ-123, respectively (P<0.05 for difference), and 0.28+/-0.07 mg/g in rings in which the endothelium had been removed. Local endothelin release is an important mechanism by which the responsiveness of the systemic vasculature to agonists may be preserved during hypoxia.
Copyright 1998 Academic Press.