Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice

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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. ; Quintao, Eder C. R. ; Passarelli, Marisa ; Nakandakare, Edna R. ; Catanozi, Sergio

• Document type: Journal article
• Source: PLoS One; v. 12, n. 5 MAY 8 2017.
• Web of Science Citations: 0

Abstract

This study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids. Aortic lipid infiltration was lower in Los-treated H-LS mice (H-LS+Los) than in normotensive (N)-LS and H-LS mice. Aortic angiotensin II type 1 (AT1) receptor content was greater in H-NS than H-LS mice and in H-LS+Hyd than H-LS+Los mice. Carboxymethyl-lysine (CML) and receptor for advanced glycation end products (RAGE) immunostaining was greater in H-LS than H-NS mice. CML and RAGE levels were lower in LS animals treated with antihypertensive drugs, and Hyd enhanced the AT1 receptor level. Hyd also increased the gene expression of F4/80 but not tumor necrosis factor-a, interleukin (IL)-1 beta, IL-6, IL-10, intercellular adhesion molecule-1 or cluster of differentiation 66. The novelty of the current study is that in a murine model of simultaneous hypertension and hyperlipidemia, the pleiotropic effect of chronic, severe sodium restriction elicited aortic damage even with reduced BP. These negative effects on the arterial wall were reduced by AT1 receptor antagonism, demonstrating the influence of angiotensin II in atherogenesis induced by a severely LS diet. (AU)

• FAPESP's process: 11/04631-0 - Advanced glycation end-products and renin-angiotensin system: impact on the development of atherosclerosis in dislipidemic mice
• Grantee: Diego Juvenal Gomes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/16164-7 - Aortic lipid infiltration in renovascular hypertensive hyperlipidemic mice elicited by dietary sodium chloride restriction improves by losartan and hydralazine
• Grantee: Fernanda Bueno Fusco
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/11084-0 - Chronic sodium chloride restriction and atherogenesis in animal model of dyslipidemia and hypertension
• Grantee: Sergio Catanozi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/19755-9 - Advanced glycation end products and renin-angiotensin system: impact on the development of atherosclerosis in dyslipidemic mice
• Grantee: Marisa Passarelli
• Support Opportunities: Regular Research Grants