ETAReceptor Antagonist Prevents Blood Pressure Elevation and Vascular Remodeling in Aldosterone-Infused Rats

Abstract

Abstract—Increased endothelin-1 may be associated with elevation of blood pressure (BP) and promotion of vascular hypertrophy, especially in salt-sensitive hypertension. Mineralocorticoid hypertension has been associated with activation of the endothelin system. We evaluated whether in aldosterone-infused rats the selective endothelin type A receptor-antagonist BMS 182874 prevents BP elevation and vascular hypertrophy. Rats were infused with aldosterone (0.75 μg/h) subcutaneously via a mini-osmotic pump and were offered 1% NaCl in the drinking water±BMS 182874 (40 mg/kg in food) for 6 weeks. Systolic BP was monitored by the tail-cuff method, and vascular changes of mesenteric arteries were evaluated using a pressurized myograph. Aldosterone-infusion significantly increased BP to 151±7 mm Hg compared with controls (108±4 mm Hg,P<0.01). BMS 182874 normalized BP (117±4 mm Hg). Media cross-sectional area of aorta was significantly increased by aldosterone infusion (P<0.05), and BMS treatment normalized it (P<0.001). Aldosterone infusion increased media width and media-to-lumen ratio of mesenteric resistance arteries (17.6±0.4 μm and 7.5±0.4%) compared with controls (14.2±0.5 μm,P<0.01, and 5.9±0.1%,P<0.05). BMS 182874 normalized media and media-to-lumen ratio (15.1±0.6 μm and 5.7±0.1%, bothP<0.01). In conclusion, the endothelin type A receptor antagonist attenuated BP elevation and prevented vascular remodeling or hypertrophy of aorta and mesenteric resistance arteries in aldosterone-infused rats. These results suggest a role for endothelin-1 in BP elevation and structural alterations of large and small vessels in aldosterone and salt-induced hypertension.