Vascular Endothelin-1 Gene Expression and Effect on Blood Pressure of Chronic ET A Endothelin Receptor Antagonism After Nitric Oxide Synthase Inhibition With L- NAME in Normal Rats

Background Vascular expression of the endothelin-1 gene may be associated with severe vascular hypertrophy. Because in rats, inhibition of NO synthase with the l -arginine analogue N ω -nitro- l -arginine methyl ester (L-NAME) induces blood pressure elevation associated with little cardiovascular hypertrophy, we studied vascular endothelin-1 gene expression in L-NAME–treated rats and the effects of chronic endothelin antagonism. Methods and Results Sprague-Dawley rats received 100 mg·kg −1 ·d −1 L-NAME in their drinking water for 3 weeks. Systolic blood pressure rose to 189±3 mm Hg ( P