Recently,
aldosterone has been shown to activate local renin-angiotensin system in vitro. To elucidate the potential role of local renin-angiotensin system in
aldosterone-induced cardiovascular injury, we investigated the effects of selective
mineralocorticoid receptor (MR) antagonist
eplerenone (EPL),
angiotensin (Ang) II type 1 receptor antagonist
candesartan (ARB), and
superoxide dismutase mimetic
tempol (TEM) on the development of
hypertension,
vascular injury, oxidative stress, and inflammatory-related gene expression in
aldosterone-treated hypertensive rats. The increased systolic blood pressure and vascular inflammatory changes were attenuated by cotreatment either with EPL, ARB, or TEM.
Aldosterone increased
angiotensin-converting enzyme expression in the aortic tissue; its effects were blocked by EPL but not by ARB or TEM.
Aldosterone also increased Ang II contents in the aortic tissue in the presence of low circulating Ang II concentrations.
Aldosterone induced expression of various inflammatory-related genes, whose effects were abolished by EPL, whereas the inhibitory effects of ARB and TEM varied depending on the gene.
Aldosterone caused greater accumulation of the
oxidant stress marker 4-hydroxy-2-neonenal in the endothelium; its effect was abolished by EPL, ARB, or TEM.
Aldosterone increased
mRNA levels of reduced
nicotinamide adenine dinucleotide phosphate oxidase components; their effect was abolished by EPL, whereas ARB and TEM decreased only the p47phox
mRNA level but not that of p22phox or gp91phox. The present findings suggest that the Ang II-dependent pathway resulting from vascular
angiotensin-converting enzyme up-regulation and Ang II-independent pathway are both involved in the underlying mechanisms resulting in the development of
hypertension, vascular
inflammation, and oxidative stress induced by
aldosterone.