Background: The prevalence of hypertension is rising alongside obesity rates. High-fructose corn syrup and high sodium intake are linked to metabolic disorders, cardiovascular morbidity, hypertension, aortic stiffness, and diastolic dysfunction. The sex-specific responses to these dietary factors and the role of sex hormones in salt-sensitive hypertension and fructose-induced cardiovascular dysfunction remain unclear.
Aim: The study aims to examine the impact of a fructose-rich diet, with or without high salt, on blood pressure regulation, cardiac function, and molecular remodelling in Dahl salt-sensitive (DSS) rats. Additionally, we explored the influence of sex hormones by comparing male, females with intact ovaries and ovariectomized (OVX) Dahl salt sensitive (DSS) rats.
Methods: The study utilized 60 female and 30 male DSS rats, aged 10 weeks, where 15 females underwent OVX before the diet intervention. The diet intervention groups were given chow with 6% NaCl and 10% fructose in drinking water for 9 weeks: male-NaCl (DSSM-NaCl), female-NaCl (DSSF-NaCl), and female OVX-NaCl (DSS-OVX-NaCl). Control groups received regular chow with 10% fructose water: male (DSSM), female (DSSF), ovariectomized female (DSS-OVX). LV assessment was conducted using echocardiography at baseline and at endpoint, using a short axis view (SAX) and M-mode imaging. Rats were euthanized for LV biopsies, and gene expression was analyzed using RT-qPCR. Echocardiography and gene data were analyzed using two-way ANOVA multiple comparison test. For ovariectomy and echocardiography, we used gaseous anaesthesia with isoflurane, (4% induction and 1.8 % maintenance).
Results. Ovariectomized rats gained more weight than intact females, but echocardiography showed no significant LV functional differences. However, LV mass and wall thickness increased in ovariectomized groups, especially with salt treatment. Males differed significantly in LV functional and morphological parameters from females.
When analyzing genes related to heart function in LV tissue, we found that beta myosin heavy chain mRNA expression levels were significantly upregulated in both OVX female groups (DSS-OVX and DSS-OVX-NaCl) compared to the DSSF group. Atrial natriuretic factor mRNA expression was upregulated in the DSS-OVX, DSS-OVX-NaCl and DSS-M-NaCl group compared to the DSSF group. Notably, brain natriuretic peptide mRNA expression level was significantly higher only in DSS-OVX-NaCl group.
In terms of genes related to fibrosis and inflammation, monocyte chemoattractant protein-1 mRNA expression was slightly elevated in salt treated female groups. Additionally, TIMP metalloproteinase inhibitor 1 mRNA expression were upregulated in the DSS-OVX-NaCl and DSS-M-NaCl group as compared to DSSF group. Interestingly, transforming growth factor β2 mRNA expression was significantly higher in DSS-OVX, DSS-OVX-NaCL and DSSM-NaCl groups.
Furthermore, genes encoded by the mitochondrial genome, such as mitochondrially encoded cytochrome C oxidase I and cytochrome b (subunit of complex III) MT-CYB exhibited changes in expression across all salt-treated groups compared to intact females. Peroxisome proliferator activated receptor coactivator 1 beta mRNA expression was significantly higher only in DSS-OVX-NaCl group.
Conclusion. Ovariectomy in female DSS rats leads to gene expression and cardiac morphology changes, intensified by salt. Males exhibit distinct cardiac responses, indicating sex hormones' role in cardiovascular outcomes. The study underscores the complex relationship between diet, sex hormones, and cardiovascular health in hypertension.