Abstract | AIMS: METHODS AND RESULTS: A hypertensive model was established in uninephrectomized Wistar rats using DOCA- salt. After SBP stabilization, DOCA- salt rats were divided into two groups: DOCA- salt (control) and DOCA- salt treatment with ROSTA (1 mg/kg per day gavage, 3 weeks). The SBP was measured using the tail-cuff method, and vascular function was assessed in mesenteric-resistance arteries (MRAs) using a wire myograph. Nitric oxide and reactive oxygen species production were investigated. Western blot was performed to quantify protein expression. Our results indicated that ROSTA treatment decreased SBP, improved acetylcholine-induced relaxation via enhanced nitric oxide synthesis and bioavailability, decreased superoxide anion generation from NAD(P)H oxidase and cyclooxygenase-2 and reduced cytoplasmic tyrosine kinase Src phosphorylation without changes in NaKATPase activity in MRA from DOCA- salt rats. CONCLUSION: This study reports the critical role of endogenous ouabain in volume-dependent hypertension. In MRA from DOCA- salt rats, the binding of endogenous ouabain to NaK- ATPase results in downstream c-SRC activation, oxidative stress and endothelial dysfunction. Endogenous ouabain is a putative target for the treatment of hypertension, and ROSTA may represent a novel therapeutic approach.
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Authors | Camilla F Wenceslau, Luciana V Rossoni |
Journal | Journal of hypertension
(J Hypertens)
Vol. 32
Issue 3
Pg. 542-54
(Mar 2014)
ISSN: 1473-5598 [Electronic] England |
PMID | 24309491
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Androstanols
- Antihypertensive Agents
- Sodium Chloride, Dietary
- Ouabain
- Desoxycorticosterone Acetate
- Cyclooxygenase 2
- Ptgs2 protein, rat
- NADPH Oxidases
- src-Family Kinases
- Sodium-Potassium-Exchanging ATPase
- rostafuroxin
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Topics |
- Androstanols
(pharmacology)
- Animals
- Antihypertensive Agents
(pharmacology)
- Blood Pressure
(drug effects, physiology)
- Cyclooxygenase 2
(metabolism)
- Desoxycorticosterone Acetate
(toxicity)
- Endothelium, Vascular
(drug effects, physiopathology)
- Humans
- Hypertension
(drug therapy, etiology, physiopathology)
- Male
- Mesenteric Arteries
(drug effects, physiopathology)
- NADPH Oxidases
(metabolism)
- Ouabain
(antagonists & inhibitors, metabolism)
- Oxidative Stress
(drug effects)
- Rats
- Rats, Wistar
- Signal Transduction
(drug effects)
- Sodium Chloride, Dietary
(toxicity)
- Sodium-Potassium-Exchanging ATPase
(metabolism)
- Vascular Resistance
(drug effects)
- Vasodilation
(drug effects)
- src-Family Kinases
(metabolism)
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