Hypertension, RAS, and gender: what is the role of aminopeptidases?

Hypertension is the major risk factor for coronary heart disease, stroke, and renal disease. Also, it is probably the most important risk factor for peripheral vascular disease and vascular dementia. Although hypertension occurs in both men and women, gender differences have been observed. However, whether sex hormones are responsible for the observed gender-associated differences in arterial blood pressure, and which is their mechanism of action, remains unclear. Local and circulating renin-angiotensin systems (RAS) are examples of systems that may be involved in the pathogenesis of hypertension. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. This review will briefly summarize what is known about gender differences in RAS-regulating aminopeptidase activities, their relationship with sex hormones, and their potential role in controlling blood pressure acting through local and circulating RAS.