Affiliation:
1. From the Canadian Institutes of Health Research (CIHR) Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal (IRCM), University of Montreal, Montreal, Quebec, Canada.
Abstract
Endothelin A (ET
A
) receptor blockade has prevented vascular remodeling in aldosterone and salt-induced hypertension. To evaluate effects of the ET
A
receptor antagonist, BMS 182874, compared with the aldosterone antagonist, spironolactone, on vascular remodeling in aldosterone-infused rats not exposed to a high salt diet, Sprague-Dawley rats were infused subcutaneously with aldosterone (0.75 μg/h) and treated with BMS 182874 (40 mg · kg
−1
· d
−1
), spironolactone, or hydralazine (both 25 mg · kg
−1
· d
−1
) while receiving a normal salt diet for 6 weeks. Aldosterone increased systolic BP (
P
<0.01), plasma endothelin (3.33±0.32 versus 1.85±0.40 pmol/L in control,
P
<0.05), systemic oxidative stress as shown by plasma thiobarbituric acid–reacting substances and vascular nicotinamide adenine dinucleotide phosphate (NADPH) activity. Aldosterone increased small artery media thickness (17.7±0.9 versus 13.6±0.8 μm in control,
P
<0.05) and media/lumen ratio (7.6±0.4 versus 5.5±0.4% in control,
P
<0.05), with growth index of 21% indicating hypertrophic remodeling. Laser confocal microscopy showed increased collagen and fibronectin deposition and intercellular adhesion molecule-1 (ICAM-1) content in the vessel wall of aldosterone-infused rats. The 3 treatments lowered BP, although hydralazine was slightly less effective. BMS 182874 and spironolactone decreased oxidative stress, normalized the hypertrophic remodeling, decreased collagen and fibronectin deposition, and reduced ICAM-1 abundance in the vascular wall of aldosterone-infused rats, whereas hydralazine only reduced NADPH activity in aorta but did not affect the remaining parameters. Vascular remodeling of small arteries occurs in aldosterone-infused rats exposed to a normal salt diet and may be mediated in part by ET-1 via stimulation of ET
A
receptors. Endothelin blockade may exert beneficial effects on vascular remodeling, fibrosis, oxidative stress, and adhesion molecule expression in aldosterone-induced hypertension.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
211 articles.
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