(Hypertension. 2001;37:1444.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
ETA Receptor Antagonist Prevents Blood Pressure Elevation and Vascular Remodeling in Aldosterone-Infused Rats
From the Clinical Research Institute of Montreal, University of Montreal (J.B.P., E.L.S.), Montreal, Quebec, Canada; and Samsung Cheil Hospital, Sungkyunkwan University School of Medicine (J.B.P.), Seoul, Korea.
Correspondence to Ernesto L. Schiffrin, MD, PhD, FRCPC, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, Canada H2W 1R7. E-mail schiffe{at}ircm.qc.ca
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%, 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-1 in BP elevation and structural alterations of large and small vessels in aldosterone and salt-induced hypertension.
Key Words: hypertension, sodium-dependent • endothelin • blood vessels • aorta • arteries • hypertrophy
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