Role of sympathetic tone in BSO-induced hypertension in mice.
ABSTRACT We investigated the contribution of the sympathetic tone to the hypertension induced by chronic administration of buthionine sulfoximine (BSO) and characterized this model in mice.
Three experiments were performed. In experiment I, four groups of CBA-C57 male mice were used: controls and three groups that received oral BSO at 5, 10, or 20 mmol/l. In experiment II, the alpha(1)-adrenergic blocker prazosin was orally administered (10 mg/100 ml) to control and BSO-treated mice. All treatments were maintained for 5 weeks. Body weight (BW), tail blood pressure (BP), and heart rate (HR) were measured weekly. Direct mean arterial pressure (MAP) and morphological, metabolic, plasma, and renal variables were measured at the end of the experiments. In experiment III, the acute response of MAP and HR to the ganglionic blocker pentolinium (10 mg/kg intravenous) was used to further evaluate the sympathetic contribution to BP and HR in control and BSO-treated mice.
BSO produced dose-related increases in BP (control, 115 +/- 0.5; BSO-5, 141 +/- 0.5; BSO-10, 151 +/- 0.9; BSO-20, 163 +/- 1.1 mm Hg) and HR and augmented plasma noradrenaline, brainstem isoprostane levels, and total urinary isoprostane excretion. BSO did not produce cardiac hypertrophy and did not modify metabolic or plasma variables, or creatinine clearance, proteinuria, or renal morphology. Chronic prazosin markedly reduced MAP (control, 101 +/- 4.7; prazosin, 95 +/- 1.29; BSO-10, 130 +/- 2.9; BSO-10 +/- prazosin, 98 +/- 0.9) and HR. Acute pentolinium produced a greater percentage MAP (control, 43 +/- 4.2; BSO-10, 66 +/- 4.5) and HR decrease in BSO-treated mice vs. controls.
Sympathetic tone plays a major role in the increased BP and HR of BSO hypertensive mice.
[Show abstract] [Hide abstract]
ABSTRACT: This study evaluated the effects of the pro-oxidant buthionine sulfoximine (BSO) and of the interaction between BSO and TETRAC, an antagonist of αvß3 integrin, on tumor development and aminopeptidase (AP) activity in a murine model of implanted Lewis's carcinoma. Male CBA-C57 mice were untreated (controls) or treated with BSO (222 mg/100 mL in drinking water), TETRAC (10 mg/kg/day, i.p.), or BSO + TETRAC. BSO for 28 days and TETRAC were given for the last 20 days. Mice were subcutaneously inoculated with 1 × 10(6) Lewis carcinoma 3LL cells into the dorsum. Study variables were tumor weight (TW); Hb, as index of tumor-mediated angiogenesis; vascular endothelial growth factor (VEGF) protein abundance; protein carbonyl content; α-tubulin abundance; and GluAp, AlaAp, and AspAp activities. BSO produced a major decrease in TW (203 ± 18 mg) with respect to controls (365 ± 26) and a reduction in Hb content. The TETRAC group also showed marked reductions in TW (129 ± 15) and Hb concentration associated with a reduced VEGF content. The BSO + TETRAC group showed a major TW reduction (125 ± 13); although, the difference with the TETRAC group was not significant. BSO treatment increased protein carbonyl and tubulin abundance in comparison to controls. The activity of all APs was increased in the three experimental groups and was strongly and negatively correlated with TW. In conclusion, administration of BSO reduced the TW, which inversely correlated with protein carbonyl content, suggesting a loss of microtubule polymerization. The finding of a negative correlation between TW and AP activity opens up new perspectives for the study of APs as tumor growth modulators.Tumor Biology 05/2014; 35(8). DOI:10.1007/s13277-014-2046-2 · 2.84 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aging populations. Although senile plaques and neurofibrillary tangles are well-established hallmarks of AD, changes in cerebral white matter correlate with cognitive decline and may increase the risk of the development of dementia. We used the triple transgenic (3xTg)-AD mouse model of AD, previously used to show that white matter changes precede plaque formation, to test the hypothesis that MRI detectable changes occur in the corpus callosum, external capsule and the fornix. T2-weighted and diffusion tensor magnetic resonance imaging and histological stains were employed to assess white matter in older (11-17months) 3xTg-AD mice and controls. We found no statistically significant changes in white matter between 3xTg-AD mice and controls, despite well-developed neurofibrillary tangles and beta amyloid immunoreactive plaques. Myelin staining was normal in affected mice. These data suggest that the 3xTg-AD mouse model does not develop MRI detectable white matter changes at the ages we examined.Magnetic Resonance Imaging 08/2013; 31(9). DOI:10.1016/j.mri.2013.06.013 · 2.02 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Oxidative stress contributes to the development of several cardiovascular diseases, including diabetes, renal insufficiency, and arterial hypertension. Animal studies have evidenced the association between higher blood pressure (BP) and increased oxidative stress, and treatment with antioxidants has been shown to reduce BP, while BP reduction due to antihypertensive drugs is associated with reduced oxidative stress. In 2000, it was first reported that oxidative stress and arterial hypertension were produced in normal Sprague-Dawley rats by oral administration of buthionine sulfoximine (BSO), which induces glutathione (GSH) depletion, indicating that oxidative stress may induce hypertension. The contribution of several potential pathogenic factors has been evaluated in the BSO rat model, the prototype of oxidative stress-induced hypertension, including vascular reactivity, endothelium-derived factors, renin-angiotensin system activity, TXA(2)-PGH(2) production, sodium sensitivity, renal dopamine-induced natriuresis, and sympathetic tone. This review summarizes the main factors implicated in the pathogenesis of BSO-induced hypertension and the alterations associated with GSH depletion that are related to renal function or BP control.American Journal of Hypertension 01/2012; 25(6):629-35. DOI:10.1038/ajh.2011.240 · 3.40 Impact Factor