Sex differences in the developmental programming of hypertension

Abstract

Experimental models of developmental programming provide proof of concept and support Barker's original findings that link birthweight and blood pressure. Many experimental models of developmental insult demonstrate a sex difference with male offspring exhibiting a higher blood pressure in young adulthood relative to their age-matched female counterparts. It is well recognized that men exhibit a higher blood pressure relative to age-matched women prior to menopause. Yet, whether this sex difference is noted in individuals born with low birthweight is not clear. Sex differences in the developmental programming of blood pressure may originate from innate sex-specific differences in expression of the renin angiotensin system that occur in response to adverse influences during early life. Sex differences in the developmental programming of blood pressure may also involve the influence of the hormonal milieu on regulatory systems key to the long-term control of blood pressure such as the renin angiotensin system in adulthood. In addition, the sex difference in blood pressure in offspring exposed to a developmental insult may involve innate sex differences in oxidative status or the endothelin system or may be influenced by age-dependent changes in the developmental programming of cardiovascular risk factors such as adiposity. Therefore, this review will highlight findings from different experimental models to provide the current state of knowledge related to the mechanisms that contribute to the aetiology of sex differences in the developmental programming of blood pressure and hypertension.

Keywords: blood pressure; endothelin; oxidative stress; renal nerves; renin angiotensin system; sex hormones.

Figure 1

Potential mechanisms by which a developmental insult differentially programs the long-term control of blood pressure in males (a) and females (b). Mechanisms may be due to the influence of the hormonal milieu on the renin angiotensin system (a and b), due to innate sex differences in production of reactive oxygen species or endothelin (a and b), or impacted by increased susceptibility that occurs with age and the development of age-dependent increases in adiposity leading to activation of the sympathetic renal nerves (b). The fetus also exhibits innate sex differences in expression of the intrarenal renin angiotensin system which may (a and b) or may not reduce nephron number (b).

Figure 1

Potential mechanisms by which a developmental insult differentially programs the long-term control of blood pressure in males (a) and females (b). Mechanisms may be due to the influence of the hormonal milieu on the renin angiotensin system (a and b), due to innate sex differences in production of reactive oxygen species or endothelin (a and b), or impacted by increased susceptibility that occurs with age and the development of age-dependent increases in adiposity leading to activation of the sympathetic renal nerves (b). The fetus also exhibits innate sex differences in expression of the intrarenal renin angiotensin system which may (a and b) or may not reduce nephron number (b).