Blunted sympathetic neurovascular transduction during normotensive pregnancy

Abstract

Key points Normotensive pregnancy is associated with elevated sympathetic nervous system activity yet normal or reduced blood pressure. It represents a unique period of apparent healthy sympathetic hyperactivity. The present study models the blood pressure and heart rate (ECG R–R interval) responses to fluctuations in sympathetic nervous system activity aiming to understand neurocardiovascular transduction. The reported data clearly demonstrate that transduction of sympathetic nervous system signalling to systemic cardiovascular outcomes is reduced in normotensive pregnancy. These data are important for understanding how blood pressure regulation adapts during normotensive pregnancy and set the foundation for exploring similar mechanisms in hypertensive pregnancies. Abstract Previously, we described sympathetic nervous system hyperactivity yet decreased blood pressure responses to stress in normotensive pregnancy. To address the hypothesis that pregnant women have blunted neurocardiovascular transduction we assessed the relationship between spontaneous bursts of sympathetic nerve activity (SNA) and fluctuations in mean arterial blood pressure and R–R interval. Resting SNA, blood pressure and ECG were obtained in pregnant (third trimester, n = 18) and non‐pregnant (n = 18) women matched for age and pre‐/non‐pregnant body mass index. Custom software modelled beat‐by‐beat pressure (photoplethysmography) and R–R interval in relation to sequences of SNA bursts and non‐bursts (peroneal microneurography). Sequences were grouped by the number of bursts and non‐bursts [singlets, doublets, triplets and quadruplet (four or more)] and mean blood pressure and R–R interval were tracked for 15 subsequent cardiac cycles. Similar sequences were overlaid and averaged. Peak mean pressure in relation to sequences of SNA was reduced in pregnant vs. non‐pregnant women (doublets: 1.6 ± 1.1 mmHg vs. 3.6 ± 3.1 mmHg, P < 0.05; triplets: 2.4 ± 1.2 mmHg vs. 3.4 ± 2.1 mmHg, P < 0.05; quadruplets: 3.0 ± 1.0 mmHg vs. 5.5 ± 3.7 mmHg, P < 0.05). The nadir R–R interval following burst sequences was also smaller in pregnant vs. non‐pregnant women (singlets: −0.01 ± 0.01 s vs. −0.04 ± 0.04 s, P < 0.05; doublets: −0.02 ± 0.03 s vs. −0.05 ± 0.04 s, P < 0.05; triplets: −0.02 ± 0.01 s vs. −0.07 ± 0.04 s, P < 0.05; quadruplets: −0.01 ± 0.01 s vs. −0.09 ± 0.09 s, P < 0.05). There were no differences between groups in the mean arterial pressure and R–R interval responses to non‐burst sequences. Our data clearly indicate blunted systemic neurocardiovascular transduction during normotensive pregnancy. We propose that blunted transduction is a positive adaptation protecting pregnant women from the cardiovascular consequences of sympathetic hyperactivity.

Sympathetic nervous system activity and reactivity in women with gestational diabetes mellitus

“…The changes in blood pressure following hyperoxia were minimal and not statistically significant among the groups. In conjunction with a significant decrease in SNA, these findings suggest that neurovascular transduction may differ during sympathetic activation versus deactivation, as observed previously in normotensive normoglycemic women (Steinback et al, 2019).…”

The physiological effect of early pregnancy on a woman’s response to a submaximal cardiopulmonary exercise test

“…Hereby we assume the longer time to full recovery of hemodynamic parameters in our pregnant population to be an indicator of less compensatory reserves during early pregnancy due to increased SV and CO in rest (Cornette et al., 2014). Also, HR recovery is a reflection of autonomic function, which is known to be altered during late pregnancy (Steinback et al., 2019).…”

Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency?

“…Though obtained from correlational analyses, these studies suggest that adrenergic sensitivity can undergo compensatory modifications to counteract higher resting MSNA (or vice versa). These mechanistic findings are often suggested to explain the association between resting sympathetic transduction of BP and MSNA (4,7,8,11). However, increases in both the frequency of sympathetic bursts and the amplitude of bursts are known to increase norepinephrine release (14).…”

“…regional vascular conductance). In particular, a number of recent studies have employed signal-averaging methods (4)(5)(6)(7)(8)(9)(10)(11), whereby the effects of each MSNA burst (or non-burst cardiac cycles) on hemodynamic variables (e.g. blood pressure [BP]) are tracked for 10-15 subsequent cardiac cycles (termed resting sympathetic transduction of BP).…”

“…This is an important consideration given that 1) current analyses of sympathetic transduction of BP and the sympathetic transduction slope fail to integrate the prevailing level of resting MSNA, and 2) the majority of evidence has observed a negative association between the neural stimulus and transduction response, such that sympathetic transduction of BP and the sympathetic transduction slope are lower in individuals with high resting MSNA burst frequency (4, 6-8, 11, 12). The majority of work has ascribed this negative relationship as a compensatory change to help maintain normal BP (4,(6)(7)(8)11). However, high resting MSNA burst frequency has also been described as a limitation towards quantifying resting sympathetic transduction of BP (12, 21) and thought to prevent its use in individuals with high resting MSNA (3,21,22).…”