Sex and the renin-angiotensin system: inequality between the sexes in response to RAS stimulation and inhibition

Abstract

The purpose of this review is to examine sex differences in response to stimulation and inhibition of the renin-angiotensin system (RAS). The RAS plays a prominent role in the development of chronic renal disease, and there are known sex differences not only in the expression level of components of the RAS but also in how males and females respond to perturbations of the RAS. In men, renal injury increases in parallel with increased activation of the RAS, while in women, increases in ANG II do not necessarily translate into increases in renal injury. Moreover, both epidemiological and experimental studies have noted sex differences in the therapeutic benefits following angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment. Despite these differences, RAS inhibitors are the most commonly prescribed drugs for the treatment of chronic renal disease, irrespective of sex. This review will examine how males and females respond to stimulation and inhibition of the RAS, with a focus on renal disease.

Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport

“…All work with animals was conducted according to an Institutional Animal Care and Use Committee-approved protocol at the Yale School of Medicine. Only female mice were used in this study to avoid the influences of the gender difference in ANG II activity and its receptor expressions (42). The breeding pairs of AT 1a knockout (KO) mice (AT1a ϩ/Ϫ ) were purchased from Jackson Labs (Bar Harbor, ME), and both wild-type (WT) and AT1a Ϫ/Ϫ mice were reproduced and housed at the Yale University Animal Care facility in New Haven, CT.…”

Sex-Specific Influence of Angiotensin Type 2 Receptor Stimulation on Renal Function

“…1 Alarmingly, sex-related differences have also been reported in the efficacy of current cardiovascular therapies, 2,3 with poorer treatment outcomes commonly reported in women. 3 The development of sex-specific approaches for the treatment of hypertension and cardiovascular disease is, therefore, of utmost importance.It is well established that the kidney plays a central role in arterial pressure control. The regulation of sodium excretion by the kidney is critical to the long-term regulation of arterial pressure given its influence on body fluid volume homeostasis.…”

“…We, and others, have identified major sex differences in the expression level of various RAS components,8,9 together with differences in the male and female response to RAS activation and inhibition. 3,8,10,11 Of particular interest, increased AT 2 R expression has been identified in the kidney and vasculature of female …”

“…1 Alarmingly, sex-related differences have also been reported in the efficacy of current cardiovascular therapies, 2,3 with poorer treatment outcomes commonly reported in women. 3 The development of sex-specific approaches for the treatment of hypertension and cardiovascular disease is, therefore, of utmost importance.…”

Role of Mas receptor antagonist (A779) in renal hemodynamics in condition of blocked angiotensin II receptors in rats

“…The mechanisms underlying this difference are not clearly recognized, but it is at least understood that renin-angiotensin system (RAS) is involved (14). RAS has a major role in kidney function, and it regulates the body fluid and blood pressure gender dependently (8,13,37). RAS includes vasoconstriction and vasodilation effects in renal and systematic vascular bed depending on the angiotensin converting enzyme 1 and 2 (ACE or ACE1, ACE2) (32,43).…”