Sex-Related Differences in Hypertension

Abstract

M uch of what we understand about the regulation of arterial pressure and extracellular fluid volume has been derived from studies in men. Although the responses that can be mounted against major physiological challenges to extracellular fluid volume (hemorrhage/dehydration) are essentially similar in men and women, there are marked sex-related differences in the regulation of renal and cardiovascular physiology. These possibly underpin the greater risk of renal and cardiovascular disease (CVD) in men and, conversely, confer the relative protection from these conditions in women, at least until menopause. In recent years, advances have been made in understanding the mechanistic bases for sex-related differences in CVD and these have been reviewed in detail.1-3 Therefore, the purpose of this report is to provide an update of findings in the past few years. Sex-Specific Risk Factors and Clinical OutcomesIncreasingly, studies are incorporating sex as a factor into their analyses.Although not all studies demonstrate a sex-specific interaction, 4-7 many do, exemplifying the mantra, seek and ye shall find; this appears to be particularly true for sex-related differences in CVD. In recent years, evidence that women have smaller and stiffer hearts because of a greater collagen content has received a good deal of attention for the reason that it may explain some of the puzzling differences in clinical signs of CVD between men and women. Puntmann et al 8 examined aortic stiffness by pulse wave velocity and ventricular deformation indices using MRI both at rest and during dobutamine challenge in elderly men and women. At rest, women had greater aortic stiffness and ventricular deformation than men. Moreover, sex-related differences were observed during stress because men had increased longitudinal and circumferential ventricular deformation during dobutamine challenge, whereas women only had an increase in circumferential deformation. 8 These data suggest that differential loading of the aortic reservoir in men occurs because of increases in longitudinal and circumferential ventricular contraction, an effect independent of aortic stiffness. However, dynamic challenge with dobutamine induced only a limited response in women, because although men could improve longitudinal ventricular contraction, women could not. Russo et al 9 reported similar findings of increased arterial stiffness and wave reflection in women compared with those in men. In addition, an inverse relationship between arterial stiffness and left ventricular diastolic function was identified in both sexes. Therefore, higher arterial stiffness may contribute to the greater risk of developing heart failure in the presence of a normal ejection fraction in women. In both men and women, there is a linear increase in arterial stiffness with aging. Although women have increased arterial stiffness, this may be somewhat tempered by female sex steroids during the reproductive years. Following menopause, there is a profound acceleration in arterial stiffening, probably ...

Metabolic Syndrome: Does it Differ Between Women and Men?

“…While the prevalence of uncontrolled blood pressure was similar in men and women during treatment, women had greater improvements in systolic blood pressure as compared to men [31]. Trajectory of arterial blood pressure with age is dissimilar between men and women due to biological differences in endocrine parameters, adipose tissue morphology and distribution, and arterial stiffness [32]. Studies report anatomic differences in the vasculature and heart between men and women; women have stiffer hearts and arteries.…”

“…A sympathoexcitatory effect of progesterone and sympathoinhibitory effect of estrogen have also been described. Animal studies demonstrate a protective effect of female hormones against the development of arterial hypertension [32]. The sex hormone mediated effects are attenuated with aging, which explains the rise in hypertension in postmenopausal women.…”

GPER-1 and Estrogen Receptor-β Ligands Modulate Aldosterone Synthesis

“…(Endocrinology 155: 4296 -4304, 2014) F ertile women are at lower risk of cardiovascular (CV) events and have lower blood pressure (BP) values than age-matched men (1, 2); for example, among hypertensive patients recruited in the ONTARGET trial, women had a 22% lower risk for myocardial infarction than men (3). Therefore, estrogens can decrease BP and thereby CV risk, possibly by affecting the renin-angiotensin-aldosterone system and the sympathetic nervous system, which feature major gender-related differences (4).…”

Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor

“…A large body of evidence now exists that the RAS is differentially modulated between the sexes, and elicits sex-specific effects on renal function, including the AT 2 R (18,(25)(26)(27)(28)(29)(30). Moreover, we have previously identified significant sex differences in the postnatal ontogeny of many RAS components, at least in male and female rats (11).…”