Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in...

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Renal Physiology

Background:

• Growing interest in sex differences within the renin-angiotensin system (RAS).
• Limited understanding of gender's influence on cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity.
• This study investigates the relationship between ACE and ACE2 activity, cardiac function, and gender in spontaneously hypertensive rats (SHRs).

Purpose of the Study:

• To determine the relationship between cardiac ACE and ACE2 activity, left ventricular function, and gender in SHRs.
• To investigate the effects of gonadectomy on these parameters in male and female rats.
• To explore the impact of sex hormones on cardiac RAS components and function.

Main Methods:

• Utilized 12-week-old female and male SHRs, divided into sham and gonadectomized groups.
• Measured cardiac ACE and ACE2 activity, left ventricular function (+dP/dt, -dP/dt), and cardiac hypertrophy.
• Assessed expression of calcium handling proteins (SERCA2a, PLB) using Western blot.

Main Results:

• Male rats exhibited higher cardiac ACE and ACE2 activity and hypertrophy compared to females.
• Orchiectomy decreased enzyme activity and hypertrophy; ovariectomy increased hypertrophy and ACE2 activity but not ACE activity.
• Gonadectomy altered cardiac function parameters (+dP/dt, -dP/dt) differently between sexes, with ovariectomy increasing PLB and the PLB/SERCA2a ratio in females.

Conclusions:

• Ovariectomy exacerbates cardiac hypertrophy, ACE2 activity, and hemodynamic dysfunction, alongside increased PLB expression.
• Testosterone removal in males shows opposite effects on RAS components compared to females.
• Gender and sex hormones play a critical role in regulating cardiac RAS and function in SHRs.