Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors

Abstract

Young women tend to have lower blood pressure, and less risk of hypertension, compared to young men. As people age, both blood pressure and the risk of hypertension increase in both sexes; this occurs most strikingly in women after menopause. However, the mechanisms for these influences of sex and age remain incompletely understood. In this review we are specifically interested in the interaction between neural (sympathetic nerve activity; SNA) and haemodynamic factors (cardiac output, blood pressure and vascular resistance) and how these change with sex and age. While peripheral vascular SNA can vary 7- to 10-fold among normotensive young men and women, it is reproducible in a given individual. Surprisingly, higher levels of SNA are not associated with higher blood pressures in these groups. In young men, high SNA is associated with higher total peripheral vascular resistance (TPR), and appears to be balanced by lower cardiac output and less peripheral vascular responsiveness to adrenergic stimulation. Young women do not exhibit the SNA-TPR relationship. Recent evidence suggests that β-adrenergic vasodilatation offsets the vasoconstrictor effects of α-adrenergic vasoconstriction in young women, which may contribute to the generally lower blood pressures in this group. Sympathetic nerve activity increases with age, and in groups over 40, levels of SNA are more tightly linked to levels of blood pressure. The potentially protective β-adrenergic effect seen in young women appears to be lost after menopause and probably contributes to the increased blood pressure and increased risk of hypertension seen in older women.

Figure 1. The relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) in young men and women (<40 years; top panels) and older men and women (>40 years; bottom panels)

The relationship between MSNA and MAP becomes positive in older men and women. Taken from Narkiewicz et al. (2005).

Figure 2. The relationship of MSNA to total peripheral resistance (TPR; top panels) and cardiac output (CO; bottom panels) in young men (left) and young women (right)

MSNA (bursts per 100 heart beats) is positively related to TPR but inversely related to cardiac output in young men. Conversely, there is no relationship among MSNA, TPR and cardiac output in young women. Data taken from Charkoudian et al. (2005, 2006a,b) and Hart et al. (2009a,b, 2011).

Figure 3. The relationship between MSNA and TPR in young men, young women and postmenopausal (PM) women before (left) and during (right) systemic β-blockade with propranolol

Systemic β-blockade caused the relationship between MSNA and TPR to become positive in young women, so it was similar to that observed in young men and postmenopausal women. BB, before β-blockade. Taken from Hart et al. (2011).

Figure 4. Summary schematic representing our overall hypothesis regarding the role of sympathetic nerve activity in maintaining overall total peripheral vascular resistance (TPR) and blood pressure at rest

For a given level of resting MSNA, noradrenaline (NA) release from the sympathetic synapse can bind to α- and/or β–adrenergic receptors. The receptor that noradrenaline binds to subsequently influences how resting MSNA is transmitted into vasoconstrictor tone. The double arrow at the level of the synapse represents which receptor is primarily activated by noradrenaline in each specific group (NB: we do not know whether noradrenaline preferentially binds to the β–adrenergic receptors in young women (YW) or whether there is an increased density of those receptors). The effect of the given level of MSNA on total peripheral resistance combined with how cardiac output (CO) relates to MSNA, defines what effect resting MSNA has on resting arterial pressure. For example, young men (YM) with high MSNA (up arrow) have a high TPR and a low cardiac output (down arrow). The end result is that at rest MSNA has a minimal effect on resting blood pressure (horizontal double ended arrow) in young men. PMW, postmenopausal women; OM, older men; VSMC, vascular smooth muscle cell.