Barnes, Jill N.

Cerebrovascular reactivity (CVR) is reduced in patients with cognitive decline. Women with a history of preeclampsia are at increased risk for cognitive decline. This study examined an association between pregnancy history and CVR using a subgroup of 40 age- and parity-matched pairs of women having histories of preeclampsia (n=27) or normotensive pregnancy (n=29) and the association of activated blood elements with CVR. Middle cerebral artery velocity was measured by Doppler ultrasound before and during hypercapnia to assess CVR. Thirty-eight parameters of blood cellular elements, microvesicles, and cell–cell interactions measured in venous blood were assessed for association with CVR using principal component analysis. Middle cerebral artery velocity was lower in the preeclampsia compared with the normotensive group at baseline (63±4 versus 73±3 cm/s; P =0.047) and during hypercapnia ( P =0.013–0.056). CVR was significantly lower in the preeclampsia compared with the normotensive group (2.1±1.3 versus 2.9±1.1 cm·s·mm Hg; P =0.009). Globally, the association of the 7 identified principal components with preeclampsia ( P =0.107) and with baseline middle cerebral artery velocity ( P =0.067) did not reach statistical significance. The interaction between pregnancy history and principal components with respect to CVR ( P =0.084) was driven by a nominally significant interaction between preeclampsia and the individual principal component defined by blood elements, platelet aggregation, and interactions of platelets with monocytes and granulocytes ( P =0.008). These results suggest that having a history of preeclampsia negatively affects the cerebral circulation years beyond the pregnancy and that this effect was associated with activated blood elements.

Hypertensive pregnancy (HTNP) is a risk factor for future cardiovascular disease. Exaggerated cardiovascular responses to physical stress are also considered an independent marker of cardiovascular disease risk. However, there are limited data regarding the blood pressure (BP) responses to acute stress in women, who have a history of HTNP. Hence, the aim of the study is to compare BP responses to a physical stress in postmenopausal women with a history of HTNP to age- and parity-matched women with a history of normotensive pregnancy (NP). Beat-to-beat BP and heart rate was recorded in 64 postmenopausal women with [age = 58.5 (55.2, 62.2) yr, where values are the median, 25th percentile, and 75th percentile] and without [age = 59.4 (55.9, 62.4) yr] a history of HTNP before and during isometric handgrip (IHG) exercise (30% of maximal voluntary contraction) to fatigue. Muscle metaboreflex was measured during postexercise ischemia following IHG exercise. BP variables increased similarly in response to IHG exercise [systolic: NP = 11.5 (8.9, 17.6) %, HTNP = 11.3 (9.5, 15.9) %; diastolic NP = 11.2 (7.9, 13.3) %, HTNP = 9.5 (7.1, 14.3) %; mean blood pressure: NP = 9.8 (5.0, 13.6) %, and HTNP = 7.2 (4.4, 10.4) %] and postexercise ischemia [systolic: NP = 14.1 (10.3, 23.0) %, HTNP = 15.8 (10.6, 21.4) %; diastolic NP = 12.2 (4.8, 17.0) %, HTNP = 10.4 (5.3, 17.1) %; and mean blood pressure: NP = 11.1 (6.1, 17.9) %, HTNP = 9.4 (2.9, 14.8) %] in both groups. Although having a history of HTNP is associated with future cardiovascular disease risk, results from this study suggest that the risk may not be manifested through altered cardiovascular metaboreflex response to physical stressors.

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure ( P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women ( P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women ( P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women ( P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group ( P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.

Lower body negative pressure (LBNP) is often used to simulate blood loss in humans. It is unknown if cerebral blood flow responses to actual blood loss are analogous to simulated blood loss during LBNP. Nine healthy men were studied at baseline, during three levels of LBNP (5 min at −15, −30, and −45 mmHg), and during three levels of blood loss (333, 667, and 1,000 ml). LBNP and blood loss conditions were randomized. Intra-arterial mean arterial pressure (MAP) during LBNP was similar to that during blood loss ( P ≥ 0.42). Central venous pressure (2.8 ± 0.7 vs. 4.0 ± 0.8, 1.2 ± 0.6 vs. 3.5 ± 0.8, and 0.2 ± 0.9 vs. 2.1 ± 0.9 mmHg for levels 1, 2, and 3, respectively, P ≤ 0.003) and stroke volume (71 ± 4 vs. 80 ± 3, 60 ± 3 vs. 74 ± 3, and 51 ± 2 vs. 68 ± 4 ml for levels 1, 2, and 3, respectively, P ≤ 0.002) were lower during LBNP than blood loss. Despite differences in central venous pressure, middle cerebral artery velocity (MCAv) and cerebrovascular conductance were similar between LBNP and blood loss at each level (MCAv at level 3: 62 ± 6 vs. 66 ± 5 cm/s, P = 0.37; cerebrovascular conductance at level 3: 0.72 ± 0.05 vs. 0.73 ± 0.05 cm·s−1·mmHg−1, P = 0.53). While the slope of the MAP-MCAv relationship was slightly different between LBNP and blood loss (0.41 ± 0.03 and 0.66 ± 0.04 cm·s−1·mmHg−1, respectively, P = 0.05), time domain gain between MAP and MCAv at maximal LBNP/blood loss ( P = 0.23) and low-frequency MAP-mean MCAv transfer function coherence, gain, and phase were similar ( P ≥ 0.10). Our results suggest that cerebral hemodynamic responses to LBNP to −45 mmHg and blood loss up to 1,000 ml follow a similar trajectory, and the arterial pressure-cerebral blood velocity relationship is not altered from baseline under these conditions.

Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. Although ≈80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine whether women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared with women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (aged 18–35 years) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53; 25±4 years) and women with natural menstrual cycles (n=74; 25±4 years). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure, 89±1 versus 85±1 mm Hg, respectively; P =0.01), although MSNA was similar in both groups (MSNA burst incidence, 16±1 versus 18±1 bursts/100 heartbeats, respectively; P =0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 versus 4.7±0.2 L/min, respectively; P =0.47) and total peripheral resistance (19.2±0.8 versus 20.0±0.9 U, respectively; P =0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use when compared with naturally menstruating women in the early follicular phase.