Ps-B05-4: Comparative Effects of Renal Denervation in Different Stages of Hypertension on Cardiac, Renal, and Adipose Pathology in Dahl Salt-Sensitive Rats

Abstract

Objectives: Endocrinometabolic disorders in women of child-bearing age, including polycystic ovarian syndrome (PCOS) has contributed to increased prevalence of cardiovascular disease (CVD) risk and its attendant complications, which often degenerate to cardiovascular morbidity and mortality, that is among the leading cause of death globally. Acetate, the most abundant endogenously produced short chain fatty acid has been linked to metabolic health. However, the impact of acetate on CVD-driven pathologies in PCOS is unknown. The present study therefore hypothesized that acetate would attenuate cardiometabolic abnormalities in experimentally induced rat model of PCOS, possibly by suppression of PCSK9/NF-kB-dependent pathways. Materials and Methods:Eight-week-old female Wistar rats were allotted into four groups (n = 6) and the groups received vehicle, acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole plus acetate respectively. The administrations were done once daily by oral gavage and lasted for 21 days. Results:In letrozole-induced PCOS rats characterized with insulin resistance, glucose dysregulation, elevated plasma testosterone and decreased 17-Beta estradiol as well as degenerated ovarian follicles and reduced normal follicles. There was also a significant increase in plasma and cardiac lipid/lipoproteins, lipid peroxidation, inflammatory mediators (NF-kB and TNF-alpha), gamma-glutamyl transferase/lactate dehydrogenase and lactate content, PCSK9 and reduction in plasma and cardiac antioxidants (glutathione peroxidase and reduced glutathione) and plasma nitric oxide synthesis (eNOS and NO) compared with the control rats. In addition, immunohistochemical assessment of cardiac tissue showed severe expression of inflammasome in letrozole-induced PCOS rats compared with the control rats. Nevertheless, supplementation with acetate significantly attenuated these alterations. Conclusions:The current study demonstrates cardiac inflammation in experimentally induced PCOS, which is accompanied by elevated atherogenic lipid/ LDLc, NO-dependent oxidative stress and endothelial dysfunction and mediated by elevated levels of PCSK9 and NF-kB. The results in addition suggest that acetate attenuates PCOS-associated cardiac inflammation by suppression of PCSK9/ NF-kB-dependent mechanisms.