Chronic sodium chloride restriction and atherogenesis in animal model of dyslipidemia and hypertension

• Grant number: 13/11084-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2013
• End date: March 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sergio Catanozi
• Grantee: Sergio Catanozi
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Edna Regina Nakandakare ; Joel Claudio Heimann ; Luzia Naoko Shinohara Furukawa ; Marisa Passarelli ; Vera Luiza Capelozzi ; Walcy Paganelli Rosolia Teodoro

Abstract

Sodium chloride restriction indicated in the hypertension treatment impairs lipid and carbohydrate metabolism. Hyperlipidemia and activation of renin-angiotensin-aldosterone system enhance atherosclerosis development. Thus, angiotensin II receptor activation stimulates arterial lipid infiltration, reactive oxygen species, advanced glycated end products, inflammatory mediators, monocyte adhesion in endothelial cells and oxidized LDL macrophage uptake. In the present study, newly weaned 3-week old male LDLR knockout mice will be fed ad libitum either low sodium diet (0.15% NaCl) or normal sodium diet (1.27% NaCl). After 7 weeks clip will be placed around the right renal artery to induce renovascular hypertension. Two groups of hypertensive animals fed low sodium diet will be treated with losartan (20 mg/Kg/day) or hydralazine (15 mg/Kg/day). Thus, six experimental groups will be investigated: hypertensive normal sodium, hypertensive low sodium, hypertensive low sodium + losartan, hypertensive low sodium + hydralazine, normotensive low sodium and normotensive normal sodium. After 10 weeks, arterial blood pressure, urinary sodium excretion, plasma concentration of triglycerides, total cholesterol, nonesterified fatty acids and aldosterone will be measured. Aortic arch will be removed to measure lipid infiltration and macrophage expression of ANG II, AT1 receptor, oxidized LDL receptor (LOX-1) and CD-68. The results will allow investigating the effect of sodium restriction on atherosclerosis development in hypertensive and hyperlipidemic animal model. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FUSCO, FERNANDA B.; GOMES, DIEGO J.; BISPO, KELY C. S.; TOLEDO, VERONICA P.; BARBEIRO, DENISE F.; CAPELOZZI, VERA L.; FURUKAWA, LUZIA N. S.; VELOSA, ANA P. P.; TEODORO, WALCY R.; HEIMANN, JOEL C.; et al. Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice. PLoS One, v. 12, n. 5, MAY 8 2017. (11/04631-0, 11/16164-7, 13/11084-0, 12/19755-9)

GOMES, DIEGO JUVENAL; VELOSA, ANA PAULA; OKUDA, LIGIA SHIMABUKURO; FUSCO, FERNANDA BUENO; DA SILVA, KAROLINNE SANTANA; PINTO, PAULA RAMOS; NAKANDAKARE, EDNA REGINA; CORREA-GIANNELLA, MARIA LUCIA; WOODS, TOM; BRIMBLE, MARGARET ANNE; et al. Glycated albumin induces lipid infiltration in mice aorta independently of DM and RAS local modulation by inducing lipid peroxidation and inflammation. JOURNAL OF DIABETES AND ITS COMPLICATIONS, v. 30, n. 8, p. 1614-1621, NOV-DEC 2016. (13/11084-0, 11/04631-0, 12/19755-9, 11/16164-7, 13/02854-7, 13/23392-1)

PINTO, PAULA R.; DA SILVA, KAROLLINE S.; IBORRA, RODRIGO T.; OKUDA, LIGIA S.; GOMES-KJERULF, DIEGO; FERREIRA, GUILHERME S.; MACHADO-LIMA, ADRIANA; ROCCO, DEBORA D. F. M.; NAKANDAKARE, EDNA R.; MACHADO, UBIRATAN F.; et al. Exercise Training Favorably Modulates Gene and Protein Expression That Regulate Arterial Cholesterol Content in CETP Transgenic Mice. FRONTIERS IN PHYSIOLOGY, v. 9, MAY 8 2018. (12/19112-0, 16/15603-0, 13/11084-0, 12/12088-7, 11/15153-1, 12/18724-2, 13/02854-7, 14/07617-6, 15/21072-5)