To investigate the role of renal endothelin-1 (ET-1) synthesis in water-sodium homeostasis, we measured mRNA expressions, protein levels, enzyme activity, and receptor binding of the renal ET-1 system in a DOCA- and salt-treated rat model. Male Wistar rats were divided into control and DOCA- and salt-treated (DOCA-Salt) groups. The DOCA-Salt group received 25 mg/kg body wt DOCA and was maintain...

We have demonstrated recently [Callera, Touyz, Teixeira, Muscara, Carvalho, Fortes, Schiffrin and Tostes (2003) Hypertension 42, 811-817] that increased vascular oxidative stress in DOCA (deoxycorticosterone acetate)-salt rats is associated with activation of the ET (endothelin) system via ETA receptors. The exact source of ET-1-mediated oxidative stress remains unclear. The aim of the present ...

We investigated the potential of natural occurring antioxidant alpha-lipoic acid to prevent hypertension and hypertensive tissue injury induced by deoxycorticosterone acetate (DOCA) and salt in rats. Two weeks after the start of DOCA-salt treatment, the rats were given alpha-lipoic acid (10 or 100 mg/kg/day, s.c.) or its vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment se...

Development and progression of end-organ damage in hypertension have been associated with increased oxidative stress. Superoxide anion accumulation has been reported in deoxycorticosterone acetate (DOCA)-salt hypertension, in which endothelin-1 plays an important role in cardiovascular damage. We hypothesized that blockade of ETA receptors in DOCA-salt rats would decrease oxidative stress. Both...

Phosphatidylinositol 3-kinase (PI3K) activity is increased in aortae from deoxycorticosterone (DOCA)-salt rats and enhanced PI3K activity contributes to the arterial hyperreactivity in these animals. Because PI3K activity is increased in DOCA-salt hypertension, we postulated that phosphorylation of Akt and glycogen synthase kinase 3 (GSK-3), serine threonine kinases that are downstream of PI3K,...

BACKGROUND Renal failure is associated with adverse cardiac remodeling and sudden cardiac death. The mechanism leading to enhanced arrhythmogenicity in the cardiorenal syndrome is unclear. The aim of this study was to characterize electrophysiological and tissue alterations correlated with enhanced arrhythmogenicity in two distinct mouse models of renal failure. METHODS Thirty-week-old 129Sv ...

Cholesterol synthesis inhibitors and fibrates both exercise effects that could influence BP and renal function in hypertension. To test this issue, transit-time ultrasound flow probes, implanted optical fibers, and laser-Doppler flowmetry were used for measurements of total and regional renal blood flows in lovastatin (40 mg/kg body wt) and bezafibrate (50 mg/kg body wt) chronically treated deo...

We investigated the role of heme oxygenase (HO), adiponectin, and atrial natriuretic peptide (ANP) in uninephrectomized (UnX) deoxycorticosterone-acetate (DOCA)-salt hypertensive rats, a volume-overload model characterized by elevated endothelin-1 (ET-1), mineralocorticoid-induced oxidative/inflammatory insults, fibrosis, hypertrophy, and severe renal histopathological lesions that closely mimi...

L-carnitine is an important co-factor in fatty acid metabolism by mitochondria. This study has determined whether oral administration of L-carnitine prevents remodelling and the development of impaired cardiovascular function in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6-12; #p < 0.05 versus DOCA-salt). Uninephrectomized rats administered DOCA (25 mg every 4th day s.c.) an...

Enhanced arginase (ARG) activity has been identified as a factor that reduces nitric oxide production and impairs endothelial function in vascular pathologies. Using a gene deletion model, we investigated involvement of arginase isoforms arginase 1 and 2 (ARG1 and ARG2) in hypertension and endothelial dysfunction in a mineralocorticoid-salt mouse model. Hypertension was induced in wild type (WT...