Fructose and salt induce sex- and ovary dependent cardiac hypertrophy in Dahl salt-sensitive rats

The consumption of sugar and salt plays a pivotal role in the development of metabolic disorders, hypertension, and subsequent cardiovascular morbidity. This study investigates the influence of sex and gonadal status on early signs of cardiac remodeling in hypertensive-prone Dahl salt-sensitive (DSS) rats by comparing male, female, and ovariectomized (OVX) female rats. DSS rats were provided with 10% fructose in their drinking water and subjected to either a high-salt diet (6% NaCl) or a standard-salt diet (0.3% NaCl) for 8 weeks. Mean arterial pressure, initially 115 ± 2 mmHg at baseline across all groups, increased to 127 ± 5 mmHg with the standard-salt diet and to 156 ± 7 mmHg with the high-salt diet (p < 0.001). High-salt intake was associated with significant concentric cardiac remodeling in OVX females and males but not in intact females. In parallel with these cardiac changes, gene expression analysis of left ventricular apex samples revealed increased mRNA levels of natriuretic peptides and genes associated with fibrosis and inflammation. These findings highlight a complex interplay between diet, sex hormones, and the pathophysiology of hypertensive cardiac disease. Further, this study underscores the importance of including both sexes and to consider gonadal status in hypertensive cardiac remodeling.