Harvey, Ronée E

Intravenous dexmedetomidine infusion (selective α 2 -adrenergic receptor agonist) 1) reduced the firing probability and strength of baroreflex control over medium-sized sympathetic action potentials in muscle sympathetic nerve activity (MSNA) and 2) attenuated the transduction of MSNA bursts to changes in blood pressure (BP) by reducing the magnitude of BP responses and increasing the time to peak BP. These data suggest that neural and vascular α 2 -adrenergic mechanisms contribute to sympathetic baroreflex regulation of human BP.

AbstractMenopause is associated with vascular dysfunction. During the menopausal transition, endogenous oestradiol concentrations diminish. Oestradiol is vasoprotective because it has direct and indirect effects on the vasculature. The present study aimed to determine the effect of acute exogenous oestradiol on endothelium‐dependent, endothelium independent and β2‐adrenergic receptor‐induced vasodilatation in females. Forearm blood flow (venous occlusion plethysmography) was measured during brachial intraarterial infusions of ACh (endothelium‐dependent agonist), sodium nitroprusside (endothelium independent agonist) and terbutaline (β2‐adrenergic receptor agonist) with and without concurrent infusion of 17β‐oestradiol. Nine young premenopausal (age: 26 ± 4 years) and nine postmenopausal (PM, age: 58 ± 4 years, 8 ± 1 years post‐menopause) females completed the study. Concurrent oestradiol infusion augmented the vasodilatory response to ACh, sodium nitroprusside and terbutaline in young premenopausal (all P < 0.05) but not older postmenopausal (all P > 0.05), females. Local infusion of exogenous 17β‐oestradiol augmented endothelial and smooth muscle microvascular vasodilatation in premenopausal but not postmenopausal, females. imageKey points Menopause is associated with vascular dysfunction. Because oestradiol has vasoprotective effects, the menopause‐associated drop in oestradiol concentrations is hypothesized to contribute to vascular dysfunction during the menopause transition. The present study shows that local infusion of exogenous oestradiol augmented microvascular vasodilatation in premenopausal but not postmenopausal females.

The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.

Abstract BACKGROUND Studies demonstrate an association between aortic hemodynamics and cognitive function. The impact of pregnancy history on this association is unknown. METHODS Postmenopausal women (age 59 ± 5 years; years since last pregnancy 35 ± 3) with either a history of preeclampsia (PE; n = 34) or a history of a normotensive pregnancy (NP; n = 30) underwent cognitive testing: Letter-Number Sequencing, Digit Span, Trail Making Test, and letter and category fluency. Applanation tonometry was used to derive aortic systolic and diastolic blood pressure and augmentation index. RESULTS Distribution of cognitive scores and aortic hemodynamic measures was similar between the PE and NP groups. Principal component (PC) analysis was used to reduce the 3 aortic hemodynamic measures and the 5 cognitive variables to single summary indices, each representing a weighted average of their respective constituent variables. Using a multivariable linear model based on these PCs that adjusted for pregnancy history and body mass index, the composite index of aortic hemodynamics was associated with the summary cognitive index, whether taking into account a potential interaction with pregnancy history (P = 0.035) or not (P = 0.026) (interaction P = 0.178). Multivariable modeling of individual cognitive tests revealed a differential association for letter fluency by pregnancy history (test for interaction P = 0.023); this score correlated with the aortic hemodynamic index in the PE (partial R2 = 0.20), but not the NP (partial R2 = 0.00) group. CONCLUSIONS Elevated aortic hemodynamics may negatively impact cognitive function in postmenopausal women with specific executive functions, such as letter fluency, being impacted more by a pregnancy history of PE.

New Findings What is the central question of this study? What is the role of β2‐adrenergic receptor (β2AR) vasodilatation in older postmenopausal women as compared to premenopausal women and the role of nitric oxide (NO) in β2AR‐mediated vasodilatation in both groups of women? What is the main finding and its importance? β2AR responsiveness is blunted in postmenopausal women compared to young premenopausal women. Additionally, NO may contribute to β2AR‐mediated vasodilatation in young premenopausal women. Abstractβ2‐Adrenergic receptor (β2AR)‐mediated vasodilatation, which is partially dependent on nitric oxide (NO) formation, is blunted in men at risk for developing hypertension. However, the role of β2AR vasodilatation in hypertension pathophysiology in ageing postmenopausal women is unclear. Therefore, the goals of this study were to determine if forearm vasodilatation to the selective β2AR agonist terbutaline is blunted in older postmenopausal women (59 ± 4 years) compared to young premenopausal women (27 ± 3 years) and to assess NO contribution to β2AR‐mediated vasodilatation in both groups of women. Forearm blood flow (FBF) and forearm vascular conductance (FVC) were measured using venous occlusion plethysmography at baseline and during intra‐arterial infusions of terbutaline at 0.1–2.0 µg (100 ml tissue)−1 min−1 with and without the NO synthase inhibitor l‐NG‐monomethylarginine (l‐NMMA). Mean arterial pressure was significantly greater in postmenopausal women than in young women at baseline (P = 0.01). Baseline FBF and FVC did not differ between young and postmenopausal women (P > 0.05) and rose significantly within each group during terbutaline infusion (P < 0.05). There were significant group × dose interactions for FBF (P = 0.01) and FVC (P = 0.001), indicating vasodilator responses were lower in postmenopausal women. In young women, FVC response to the highest dose of terbutaline tended to be lower with l‐NMMA co‐infusion vs. without l‐NMMA (P = 0.05). There were no significant decreases in FBF or FVC responses to terbutaline in postmenopausal women with l‐NMMA co‐infusion (P > 0.05 for all). These data suggest that β2AR responsiveness is blunted in postmenopausal women compared to young premenopausal women, and that NO may contribute to β2AR‐mediated vasodilatation in young premenopausal women.

Preeclampsia (PE) is a hypertensive disorder of pregnancy described as a condition of excessive sympathoexcitation. PE places a woman at increased risk for lifelong hypertension and cognitive impairment. Cerebral blood velocity is blunted in response to a vasoactive stimulus in women with a history of PE. This study investigated how a sympathoexcitatory stimulus affects cerebral blood velocity in women with a history of PE. Middle cerebral artery blood velocity (MCAv) and beat-to-beat mean arterial blood pressure (MAP) were measured in postmenopausal women with a history of PE ( n = 21; age = 59 ± 5 yr) and a history of a normotensive pregnancy (NP; n = 27; age = 58 ± 4 yr), at baseline, during isometric handgrip to fatigue (IHG) followed by postexercise ischemia (PEI), and a recovery period (REC). Baseline MAP and MAP responses to IHG and PEI did not differ between groups. MCAv at baseline and throughout the stimulus was lower in PE women compared with NP women ( P < 0.05 for all). MCAv increased during IHG in both groups ( P < 0.05). This increase in MCAv was greater in PE compared with NP women during IHG and REC (IHG: PE 13 ± 2% vs. NP 9 ± 2%; REC: PE 3 ± 2% vs. NP −2 ± 2%; P < 0.05 for both). Thus, a history of PE is associated with low baseline cerebral blood velocity but an augmented response to a sympathoexcitatory stimulus. These changes in cerebral blood flow regulation may lead to an increased risk for cognitive impairment in women with a history of PE.