ETA receptor antagonist prevents blood pressure elevation and vascular remodeling in aldosterone-infused rats

Increased endothelin-l 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 EMS 182874 prevents BP elevation and vascular hypertrophy, Rats were infused with aldosterone (0.75 mug/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). EMS 182874 normalized BP (117 +/-4 mm Hg). Media cross-sectional area of aorta was significantly increased by aldosterone infusion (P <0.05), and EMS treatment normalized it (P <0.001). Aldosterone infusion increased media width and media-to-lumen ratio of mesenteric resistance arteries (17.6 +/-0.4 pm and 7.5 +/-0.4%) compared with controls (14.2 +/-0.5 mum, P<0.01, and 5.9f0.1%, P0.05). BMS 182874 normalized media and media-to-lumen ratio (15.1 +/-0.6 pm and 5.7 +/-0.1%, both P <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-l in BP elevation and structural alterations of large and small vessels in aldosterone and salt-induced hypertension.