The sympathetic nervous system in healthy and hypertensive pregnancies: physiology or pathology?

Pregnancy triggers profound cardiovascular changes to support fetal development, including a 50% increase in blood volume and a 31% rise in cardiac output. Historically, the autonomic nervous system's role in these changes was overlooked, but it is now recognized that healthy pregnancies exhibit a unique state of basal sympathetic hyperactivity. Paradoxically, this surge in sympathetic activity does not result in high blood pressure, but rather coincides with a state of systemic vasodilation and reduced peripheral vascular resistance.

Muscle sympathetic nerve activity (MSNA) is the gold standard for measuring sympathetic outflow in humans. Research consistently shows that MSNA is elevated in healthy, normotensive pregnancies compared to non-pregnant states, often beginning as early as the first trimester. The authors propose that this elevation is an adaptive mechanism rather than a pathological one, serving to regulate blood flow and vascular tone amidst the significant physiological shifts of pregnancy.

While sympathetic nerve activity is high, the functional effect on the vasculature—known as neurovascular transduction—is significantly blunted in healthy pregnancy. This means that despite the increased neural signals, the vessels do not constrict proportionally. The review suggests this may be due to complex peripheral adaptations, such as altered sensitivity or density of adrenergic receptors (e.g., alpha-1 and beta-2 receptors) and changes in the local concentrations of neurotransmitters like noradrenaline and neuropeptide Y.

In contrast to healthy pregnancies, conditions like gestational hypertension and obesity-related pregnancy complications show even higher sympathetic activity. However, the role of the sympathetic nervous system in pre-eclampsia is more nuanced and remains a point of controversy in the field. Understanding the normal neurovascular adaptation in pregnancy is essential for identifying when this system becomes maladaptive, potentially leading to pregnancy-related cardiovascular complications that remain major causes of maternal morbidity.