Eta Receptor Antagonist Prevents Blood Pressure Elevation and Vascular Hypertrophy of Resistance Arteries in Aldosterone-Infused Rats.
In salt-sensitive hypertension vascular endothelin-1 expression may be enhanced. Endothelin antagonism lowers blood pressure (BP), and reduces vascular hypertrophy. We therefore evaluated whether the selective ETA receptor antagonist BMS182874 (BMS) prevents BP elevation and vascular hypertrophy in resistance arteries of aldosterone-infused rats. Rats received subcutaneous aldosterone (0.75μg/h) and 1% sodium in drinking water ± BMS (40mg/kg in food) for 6 weeks. Systolic BP was monitored by tail cuff method, and vascular changes were evaluated using a pressurized myograph. Aldosterone-infusion significantly increased BP to 151±7mmHg compared to controls (108±4mmHg, p<0.01). BMS normalized BP (117±4mmHg, p<0.01). Aldosterone increased media width and media to lumen ratio (17.6±0.4μm and 7.5±0.4%) compared to controls (14.2±0.5μm, p<0.01 and 5.9±0.0%, p<0.05, respectively). BMS normalized media and media to lumen ratio (15.1±0.6μm and 5.7±0.1%, both p<0.01). Endothelial function assessed with acetylcholine (10-6 M) did not differ in the 3 groups. Maximal endothelin-1 (10-7M)-induced vasoconstriction was similar (58-62%) in all groups. In conclusion, the ETA receptor antagonist attenuated blood pressure elevation and prevented vascular hypertrophy of resistance arteries in aldosterone-infused rats.