Sympathetic regulation of blood pressure in normotension and hypertension: When sex matters

The sympathetic nervous system has a central role in the regulation of arterial blood pressure (BP) and in the development of hypertension in humans. Recent evidence points to differences between the sexes in the integrative mechanisms by which BP is controlled, suggesting that the development of hypertension may follow distinct pathways in women compared to men. An important aspect of sympathetic control of BP is its substantial inter-individual variability. In healthy young men, the variability in sympathetic nerve activity (SNA) is balanced by variability in cardiac output and vascular adrenergic responses, such that BP remains similar, and normal, across a several-fold range of resting SNA values. In young women, variability in resting SNA is similar to that seen in men, but the "balancing" mechanisms are strikingly different: women exhibit greater β-adrenergic vasodilation compared to men, which minimises the pressor effects of a given level of SNA. Aging is associated with increased SNA and a loss of the balancing factors seen in younger people, leading to an increased risk of hypertension in older people. Loss of oestrogen with menopause in women appears to be mechanistically linked with the decrease in β-adrenergic vasodilation, and the increased risk of hypertension in older women. Other important factors contributing to hypertension via sympathetic mechanisms are obesity and arterial stiffening, both of which increase with aging. We conclude with a discussion of important areas in which more work is needed to understand, and appropriately manage, sex-specific mechanisms in the development and maintenance of hypertension. This article is protected by copyright. All rights reserved.