Gender Differences in the Renin-Angiotensin and Nitric Oxide Systems: Relevance in the Normal and Diseased Kidney

Female gender is associated with better renal function and resistance to renal injury, suggesting that an oestrogen-based effect or increased androgenic effects are responsible. Studies in rodents have confirmed a biological basis for this, based on the differential effects of androgens and oestrogens on the normal and diseased kidney. Many researchers in the field believe that the pre-menopausal levels of oestrogen are key to the protection observed in females. The key pressor effects of the renin-angiotensin (RA) system are due to both direct vasoconstrictory properties and alterations in renal control of extracellular fluid volume. Additionally, the RA has been shown to promote diverse aspects of renal injury. RA activity is positively modulated by androgens and antagonized by oestrogens. Nitric oxide (NO) is a potent vasorelaxant with a key role in renal control of extracellular fluid homeostasis. NO can variously have both protective and deleterious effects on renal injury. Endogenous oestrogen has an anti-hypertensive effect as well as protective effects against cell and organ damage, many of which are mediated via increases in NO generation. We examine how the RA- and NO-generating systems may underpin key aspects of gender differences in normal renal function and renal disease.