Sex differences in angiotensin II- induced hypertension

Abstract

Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG IIinduced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen α receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.

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.…”

Central endogenous angiotensin-(1–7) protects against aldosterone/NaCl-induced hypertension in female rats

“…Sex differences in the development of hypertension and female protection from hypertension have been well described in animal models (14,15,28). Estrogen has been shown to downregulate components of the RAS hypertensive axis (i.e., ACE1/ANG II/AT1-R).…”

“…Taken together these results suggest that female sex hormones regulate an antihypertensive axis of the brain renin-angiotensin system involving ACE2/ANG-(1-7)/ Mas-R that plays an important counterregulatory role in protecting against the development of Aldo/NaCl-induced hypertension. aldosterone; blood pressure; angiotensin-(1-7); central nervous system SEX DIFFERENCES in the development of hypertension and cardiovascular diseases have been well described in humans and in animal models (14,15,28). Female sex hormones have been demonstrated to have beneficial effects on cardiovascular function through actions not only on the heart and vasculature, but also on the central nervous system (CNS) (21).…”

“…SEX DIFFERENCES in the development of hypertension and cardiovascular diseases have been well described in humans and in animal models (14,15,28). Female sex hormones have been demonstrated to have beneficial effects on cardiovascular function through actions not only on the heart and vasculature, but also on the central nervous system (CNS) (21).…”

Role of renin-angiotensin system in the formation of emotional state in humans

“…The effect of AT-II on neurotransmitter systems of the brain depends not only on the concentration of AT-II, but also on the function of AT-II receptors (number and binding capacity). Published data show that estradiol decreases the binding capacity of AT-II receptors and expression of AT-II receptor mRNA in the subfornical organ [14]. Estradiol probably responds to variations in the concentration of AT-II, which abolishes the direct effect of AT-II and ACE I/D polymorphism on physical aggression.…”