Endothelin-1 Regulates Tone of Isolated Small Arteries in the Rat

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Abstract
—Chronic elevation of plasma endothelin-1 (ET-1) levels has been reported in several pathological conditions. To investigate the consequences of increased circulating ET-1 on vascular responsiveness, Sprague-Dawley rats (n=16) were chronically instrumented with a minipump delivering ET-1 at a constant dose for 7 days. Plasma ET-1 levels were more than doubled in treated (0.98±0.09 pmol/L; P<.05) versus untreated sham-operated rats (0.43±0.04 pmol/L), whereas systolic arterial blood pressure increased (139±5 versus 128±4 mm Hg in untreated rats; P<.05). After rats were killed, segments of middle cerebral (MCA) and mesenteric (MES) arteries were mounted on an isometric myograph. ET-induced contraction was shifted to the right in ET-1–treated animals and not modified by BQ123 (an ETA receptor antagonist); bosentan (ETA/B receptor antagonist) prevented ET-1–induced contraction in both groups. After inhibition of nitric oxide synthase with Nω-nitro-l-arginine (L-NNA), both phenylephrine and oxymetazoli...