Sexual dimorphism and renin-angiotensin-aldosterone system (RAAS) in hypertension and left ventricular hypertrophy in Spontaneously Hypertensive Rat (SHR)

Abstract

Background: The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is linked to hypertensive left ventricular hypertrophy. Sex differences in the involvement of the RAAS in the development of hypertension and left ventricular hypertrophy are unclear, specifically in spontaneously hypertensive rats (SHRs). This study aimed to investigate the sexual difference in the RAAS effects on hypertension and ventricular remodelling in spontaneously hypertensive rats (SHRs). Methods: Thirty SHRs and Wistar Kyoto rats (WYKs) were assigned to four groups, namely; male SHR (n=8), female SHR (n=8), male WKY (n=7), and female WKY (n=7). Body weight, blood pressure and echocardiography parameters were measured before termination. Concentrations of RAAS parameters were measured using enzyme-linked immunosorbent assays (ELISA) at termination (after 7 months). The picrosirius red stain was used to determine collagen content in the left ventricle. Results: SHRs, in comparison to WKYs, had significantly higher blood pressure, greater heart and left ventricular mass, greater heart wall thickness, greater area of collagen and impaired left ventricular relaxation (reduced lateral e’), and increased filling pressures (increased E/e’) (p<0.05). SHRs also had significantly reduced end- diastolic volume, stroke volume and mid-wall fractional shortening (p<0.05). Females, in comparison to males, had reduced end-diastolic volume, stroke volume and mid- wall fractional shortening but had greater physiological growth (p<0.05). Female SHRs exhibited higher conscious and anaesthetised systolic and diastolic blood pressures, along with greater plasma concentrations of angiotensin II (ANG II) compared to other groups (p<0.05). v Conclusion: Compared to WKYs, SHRs developed concentric hypertrophy, impaired diastolic and systolic function. Compared to males, females developed greater physiological left ventricular growth with lower left ventricular relaxation and systolic function. The physiological cardiac differences may partly be influenced by factors such as body weight and blood volume. Additionally, female SHRs had elevated blood pressure, which may be due to increased plasma concentrations of ANG II.