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

Abstract

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.

Altered dipeptidyl peptidase IV and prolyl endopeptidase activities in chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia

“…However, the divergent results imply that the enzyme may be differently regulated in the two conditions and as a function of gender. This phenomenon has already been reported in the case of angiotensinconverting enzymes and proposed as one of the factors which could influence cardiovascular disorders in relation to changes in the renin-angiotensin system [16].…”

Hypertension alters the function of nitrergic and sensory innervation in mesenteric arteries from female rats

“…The role of CGRP in hypertension is modulated by a number of factors including the reninangiotensin system, steroids, hormones, and so on [40,41], depending on the hypertension model. The notorious sex differences described for these factors in hypertension [42,43] could explain the sex differences observed here. However, other sex-specific genomic, tissue, and cellular characteristics cannot be ruled out in any case [10], and do require further investigation.…”

Insufficient and excessive amounts of sleep increase the risk of premature death from cardiovascular and other diseases: The Multiethnic Cohort Study

“…This result is consistent with findings from a large cross-sectional study showing increased hypertension among shorter sleeping (<6 h/day) women only (Stranges et al, 2008); as well as the Whitehall II study which reported that shorter sleeping women (≤5 h/day vs. 7 h/day), but not men, had a 19% increased risk of incident hypertension (Cappuccio et al, 2007). Mechanisms are not fully understood, but sex-specific differences in the activity of the angiotensin and renin-angiotensin systems might contribute to poorer control of hypertension in women than in men (Guarner-Lans et al, 2011; Ramírez-Expósito and Martínez-Martos, 2008; Yanes and Reckelhoff, 2011). …”