
Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice
Author(s) -
F. Fusco,
Diogo Bugano Diniz Gomes,
Kely Cristina Soares Bispo,
Veronica P. Toledo,
Denise Frediani Barbeiro,
Vera Luíza Capelozzi,
Luzia Naôko Shinohara Furukawa,
Ana Paula Pereira Velosa,
W. R. Teodoro,
Joel Cláudio Heimann,
Eder Carlos Rocha Quintão,
Marisa Passarelli,
Edna Regikandakare,
Sérgio Catanozi
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0177086
Subject(s) - endocrinology , medicine , losartan , hyperlipidemia , angiotensin ii , chemistry , angiotensin ii receptor type 1 , hydralazine , blood pressure , diabetes mellitus
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-α, interleukin (IL)-1β, 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.