DOCA‐salt hypertensive rats display decreased vascular reactivity to urotensin‐II

Abstract

IntroductionUrotensin‐II (U‐II) is a vasoconstrictor peptide and its potency can be up to 100 fold greater than that of endothelin‐1 (ET‐1). ET‐1 plays a major role in the vascular changes associated with salt‐sensitive hypertension, but the effects of U‐II in arteries from these animals have not yet been defined.ObjectiveWe hypothesized that DOCA‐salt rats have increased vascular reactivity to U‐II.Methods and ResultsWistar rats were unilaterally nephrectomyzed and deoxycorticosterone‐acetate (DOCA) (200mg/Kg) pellets were implanted. DOCA rats received water containing 1% NaCl/0.2% KCl, for 5 weeks. Aortic rings were mounted in myograph chambers and functional studies were performed. DOCA rats displayed increased systolic pressure (Control: 117±1 vs DOCA: 179±3; mmHg). Maximal contractions (mN) to U‐II were decreased in endothelium‐intact (Control: 16.6±1 vs DOCA: 8.8±1) and endothelium‐denuded (Control: 21.3±1.1 vs DOCA: 10.4±0.9) aortas from DOCA rats. This difference was abolished in endothelium‐intact vessels incubated with 10−5M urantide (U‐II antagonist) (Control: 13.5±0.9 vs DOCA: 12.7±0.9).ConclusionOur results suggest that U‐II production/release is augmented in mineralocorticoid hypertension and that decreased vascular reactivity to the peptide may represent counter‐regulatory mechanisms that limit additional vascular damage to this potent vasoconstrictor.