Abstract
We aimed to characterize circulating microparticles in association with arterial stiffness, inflammation and endothelial dysfunction in aldosterone-salt-induced hypertension in rats and to investigate the preventive effects of red wine polyphenols. Uninephrectomized male Sprague-Dawley rats were treated with aldosterone-salt (1 µg.h−1), with or without administration of either red wine polyphenols, Provinols™ (20 mg.kg−1.day−1), or spironolactone (30 mg.kg−1.day−1) for 4 weeks. Microparticles, arterial stiffness, nitric oxide (NO) spin trapping, and mesenteric arterial function were measured. Aldosterone-salt rats showed increased microparticle levels, including those originating from platelets, endothelium and erythrocytes. Hypertension resulted in enhanced aortic stiffness accompanied by increased circulating and aortic NO levels and an upregulation of aortic inducible NO-synthase, NFκB, superoxide anions and nitrotyrosine. Flow-induced dilatation was reduced in mesenteric arteries. These effects were prevented by spironolactone. Provinols™ did not reduce arterial stiffness or systolic hypertension but had effects similar to those of spironolactone on endothelial function assessed by flow-mediated vasodilatation, microparticle generation, aortic NO levels and oxidative stress and apoptosis in the vessel wall. Neither the contractile response nor endothelium-dependent relaxation in mesenteric arteries differed between groups. The in vivo effects of Provinols™ were not mediated by mineralocorticoid receptors or changes in shear stress. In conclusion, vascular remodelling and endothelial dysfunction in aldosterone-salt-mediated hypertension are associated with increased circulating microparticles. Polyphenols prevent the enhanced release of microparticles, macrovascular inflammation and oxidative stress, and microvascular endothelial dysfunction independently of blood pressure, shear stress and mineralocorticoid receptor activation in a model of hyperaldosteronism.
Highlights
Mineralocorticoid administration to uninephrectomized rats drinking a concentrated salt solution is a well known model of experimental hypertension and the degree of hypertension is dependent on the duration of the aldosterone-salt regimen
The microparticle increase was accompanied by increases in aortic stiffness, oxidative and nitrosative stresses and microvascular endothelial dysfunction as well as induction of apoptosis in the vessel wall
Of particular interest is that ProvinolsTM prevented changes in circulating microparticles, microvascular endothelial dysfunction, oxidative and nitrosative stress and apoptosis
Summary
Mineralocorticoid administration to uninephrectomized rats drinking a concentrated salt solution is a well known model of experimental hypertension and the degree of hypertension is dependent on the duration of the aldosterone-salt regimen. An increase in systolic arterial pressure (SAP) was observed after administration of aldosterone and salt for 4 weeks in rats. Key aspects of this model are the maintenance of the deleterious effect of salt in presence of relatively high levels of aldosterone and the presence of proteinuria and increased oxidative stress compared with uninephrectomized rats on a normal salt diet [1]. Eplerenone treatment has been recently shown to reduce stiffness in resistance arteries [4]. A number of studies have shown that chronic treatment with aldosterone resulted in impaired acetylcholine-induced relaxation of the aorta in both normotensive and hypertensive rats resulting from inflammatory and oxidative processes [5]
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