Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling

Pu, Q., Neves, M.F., Virdis, A., Touyz, R.M. and Schriffin, E.L. (2003) Endothelin antagonism on aldosterone-induced oxidative stress and vascular remodeling. Hypertension, 42(1), pp. 49-55. (doi: 10.1161/01.HYP.0000078357.92682.EC)

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Publisher's URL: http://dx.doi.org/10.1161/01.HYP.0000078357.92682.EC

Abstract

Endothelin A (ETA) receptor blockade has prevented vascular remodeling in aldosterone and salt-induced hypertension. To evaluate effects of the ETA 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 ETA receptors. Endothelin blockade may exert beneficial effects on vascular remodeling, fibrosis, oxidative stress, and adhesion molecule expression in aldosterone-induced hypertension.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Pu, Q., Neves, M.F., Virdis, A., Touyz, R.M., and Schriffin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
ISSN:0194-911X
ISSN (Online):1524-4563
Published Online:02 June 2003

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