T he risk of developing cardiovascular disease is lower in young women when compared with similarly aged men. [1][2][3] However, pregnancy represents a period of increased susceptibility to disordered cardiovascular regulation for women. Pregnant women have an elevated risk for orthostatic intolerance. 4,5 Moreover, ≤8% of pregnancies are associated with the development of de novo hypertension. 6 The cause of such hypertensive pregnancy disorders remains unclear, and as a result, there exist few approaches by which clinicians can predict, screen, or treat the development of the hypertensive disorders of pregnancy (gestational hypertension and preeclampsia). Previous data have shown that the vascular response to the cold pressor test (CPT) is blunted in normal pregnant women compared with women in the nonpregnant, postpartum state. 8 However, an elevated pressor response to the CPT has been observed in women with 9 or who subsequently develop 10 preeclampsia. As such, the CPT has been suggested as a simple screening tool for pregnancy-related hypertensive disorders. The mechanisms driving these divergent responses remain unknown; however, sympathetic nervous system activity is a primary determinant of the pressor response to the CPT. 11Differing vascular responses to the CPT may be mediated by altered sympathetic responses or altered translation of sympathetic activity into a vascular outcome (neurovascular transduction). Studies conducted over the past 2 decades have indicated, albeit not universally, 12 that normotensive Abstract-Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.

Blood pressure regulation during pregnancy is poorly understood. Cardiovagal baroreflex gain (BRG) is an important contributor to blood pressure regulation via its influence on heart-rate. Heart-rate fluctuations occur in response to various physiological stimuli and can be measured using heart-rate variability (HRV). It is unclear how these mechanisms operate during pregnancy, particularly related to exercise. We examined BRG and HRV prior to, during, and following prenatal exercise. Forty-three pregnant (n=10 first trimester [TM1], n=17 second trimester [TM2]; n=16 third trimester [TM3]) and 20 non-pregnant (NP) women underwent an incremental peak exercise test. Beat-by-beat blood pressure (photoplethysmography) and heart-rate (lead II ECG) were measured throughout. BRG (slope of the relationship between fluctuations in systolic blood pressure and R-R interval) and HRV (root mean square of the successive differences; RMSSD) were assessed at rest, during steady-state exercise (EX), and during active recovery. BRG decreased with gestation and was lower in TM3 compared to NP (17.9±6.9 vs 24.8±7.4 ms/mmHg, p=0.017). BRG was reduced during EX in all groups. Resting HRV (RMSSD) also decreased with gestation and was lower in TM3 compared to NP (29±17 vs 48±20 ms, p<0.001). RMSSD was blunted during EX for all groups compared to REST. During active recovery, RMSSD was further blunted compared to EX in NP, but not during pregnancy (TM1, TM2, and TM3). Compared to non-pregnant controls, pregnant women had lower BRG and HRV at rest, but comparable cardioautonomic control during both exercise and active recovery following peak exercise.

Cerebrovascular adaptation to pregnancy is poorly understood. We sought to assess cerebrovascular regulation in response to visual stimulation, hypercapnia and exercise across the three trimesters of pregnancy. Using transcranial Doppler (TCD) ultrasound, middle and posterior cerebral artery mean blood velocities (MCAvmean and PCAvmean) were measured continuously at rest and in response to (1) visual stimulation to assess neurovascular coupling (NVC); (2) a modified Duffin hyperoxic CO2 rebreathe test, and (3) an incremental cycling exercise test to volitional fatigue in non-pregnant ( n = 26; NP) and pregnant women (first trimester [ n = 13; TM1], second trimester [ n = 21; TM2], and third trimester [ n = 20; TM3]) in total 47 women. At rest, MCAvmean and PETCO2 were lower in TM2 compared to NP. PCAvmean was lower in TM2 but not TM1 or TM3 compared to NP. Cerebrovascular reactivity in MCAvmean and PCAvmean during the hypercapnic rebreathing test was not different between pregnant and non-pregnant women. MCAvmean continued to increase over the second half of the exercise test in TM2 and TM3, while it decreased in NP due to differences in ΔPETCO2 between groups. Pregnant women experienced a delayed decrease in MCAvmean in response to maximal exercise compared to non-pregnant controls which was explained by CO2 reactivity and PETCO2 level.