High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation

Abstract

Many studies have shown that risk factors that are independent of blood pressure (BP) can contribute to the development of cardiac hypertrophy (CH). Among these factors, high-salt (HS) intake was prominent. Although some studies have attempted to elucidate the role of salt in the development of this disease, the mechanisms by which salt acts are not yet fully understood. Thus, the aim of this study was to better understand the mechanisms of CH and interstitial fibrosis (IF) caused by HS intake. Male Wistar rats were divided into 5 groups according to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan (LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC) (HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and protein expression, serum aldosterone, cardiac angiotensin II, cardiac thiobarbituric acid-reactive substances, and binding of conformation-specific anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2 ventricles were measured. Based on the left ventricle transverse diameter data, the primary finding was the occurrence of significant BP-independent CH in the HS+HZ group (96% of the HS group) and a partial or total prevention of such hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group, respectively). The significant total or partial prevention of IF using all 3 treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group, respectively), and an increase in the AT1 gene and protein expression and activity in groups that developed CH, confirmed that CH occurred via the AT1 in this experimental model. Thus, this study unveiled some relevant previously unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of oxidative stress with CH in our experimental model is very interesting and stimulates further evaluation for its full comprehension.

Hydrogen Sulfide Inhibits High-Salt Diet-Induced Myocardial Oxidative Stress and Myocardial Hypertrophy in Dahl Rats

“…Long-term myocardial hypertrophy can lead to an increased myocardial oxygen consumption and reduce compliance of the heart eventually leading to heart failure or sudden death. Previous studies have shown that high-salt diet can lead to myocardial hypertrophy independent of blood pressure, thereby increasing the incidence of cardiovascular events (Mak et al, 2013; Katayama et al, 2014). However, the mechanism underlying high-salt-induced myocardial hypertrophy has not been clear yet.…”

High and Low Salt Intake during Pregnancy: Impact on Cardiac and Renal Structure in Newborns

“…The precise mechanism of these findings requires further study. However, salt restriction or overload in the heart [24,25,26] and kidneys [4] influences local renin-angiotensin system activity. These alterations may have occurred in the dams during pregnancy in the present study and influenced the local RAS in neonates via an unknown mechanism.…”

Morphological Identification of TRPC7 in Cardiomyocytes From Normal and Renovascular Hypertensive Rats [RETRACTED]

“…Ang II is known to act through the angiotensin receptor type 1 (AT1) and contributes to the development of hypertension and cardiac hypertrophy. 17 We therefore fed rats with water containing losartan, a widely used antagonist of the AT1 receptor, whereby to observe changes in the TRPC7 expression level and morphological and functional parameters. As reported elsewhere, 17 oral intake of losartan for 2 weeks significantly reduced SBP, MAP, and HeartW/BW and partially reversed hypertrophic changes in echocardiographic indexes of the left ventricle ( Fig.…”