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The endothelin-B (ETB) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ETB receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E2) on ETB receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E2 exposure modulates ETB receptor-mediated dilation in young women. Fifteen young women (24 ± 4 yr, 24 ± 3 kg/m²) completed the study. Endogenous sex hormone production was suppressed with daily administration of a gonadotropin- releasing hormone antagonist (GnRHant; Ganirelix) for 10 days; E2 (0.1 mg/day, Vivelle-Dot patch) was added back on days 4-10. We measured vasodilation in the cutaneous microcirculation (microvascular endothelial function) via local heating (42°C) on day 4 (GnRHant) and day 10 (GnRHant þ E2) using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer's (control) and ETB receptor antagonist (BQ-788, 300 nM). During GnRHant, vasodilatory responses to local heating were enhanced with ETB receptor blockade (control: 83 ± 9 vs. BQ-788: 90 ±5%CVCmax, P = 0.004). E2 administration improved vasodilation in the control site (GnRHant: 83 ± 9 vs. GnRHant þ E2: 89 ± 8%CVCmax, P = 0.036). Furthermore, cutaneous vasodilatory responses during ETB receptor blockade were blunted after E2, administration (control: 89 ± 8 vs. BQ-788: 84 ± 8%CVCmax, P = 0.047). These data demonstrate that ovarian hormones, specifically E2, modulate ETB receptor function and contribute to the regulation of microvascular endothelial function in young women. [ABSTRACT FROM AUTHOR]

Purpose: Cognition, cerebral blood flow (CBF) and its major regulator (i.e., arterial CO2), increase with submaximal exercise and decline with severe exercise. These responses may depend on fitness. We investigated whether exercise-related changes in cognition are mediated in part by concomitant changes in CBF and CO2, in ten active (26 ± 3 years) and ten inactive (24 ± 6 years) healthy adults.Methods: Participants completed two randomised sessions; exercise and a resting CO2-control-wherein end-tidal CO2 (PETCO2) was matched between sessions and clamped across conditions at exercise-associated increases (+ 3 mmHg) and hypercapnia (+ 10 mmHg). Exercise comprised inclined walking at submaximal and severe intensities. CBF was indexed using right middle cerebral artery blood velocity (MCAv). Cognition (visuomotor, switching and inhibitory response time) was measured before, during, and after exercise.Results: MCAv and its inverted-U response to exercise were comparable between groups, whereas visuomotor performance improved during submaximal exercise in the active group only (p = 0.046). Submaximal, but not severe (p = 0.33), exercise increased MCAv (p ≤ 0.03). Hypercapnia increased MCAv during the CO2-control (27 ± 12%) and during submaximal exercise (39 ± 17%; p < 0.01). Despite the acute increases in MCAv, cognition was impaired during both levels of increased PETCO2 (3-6%; p ≤ 0.04), regardless of session. Overall, resting or exercise-related changes in PETCO2 and MCAv did not associate with changes in cognition (r ≤ 0.29 ± 0.34). Fitness ([Formula: see text]O2MAX) was associated with baseline cognition (r ≥ 0.50).Conclusion: Acute increases in PETCO2 and MCAv were not associated with improved cognition. In fact, cognitive performance was impaired at both levels of increased PETCO2, regardless of session. Finally, fitter people were found to have better cognition. [ABSTRACT FROM AUTHOR]

Significance: The ability to monitor cerebral blood flow (CBF) at the bedside is essential to managing critical-care patients with neurological emergencies. Diffuse correlation spectroscopy (DCS) is ideal because it is non-invasive, portable, and inexpensive. We investigated a near-infrared spectroscopy (NIRS) approach for converting DCS measurements into physiological units of blood flow., Aim: Using magnetic resonance imaging perfusion as a reference, we investigated the accuracy of absolute CBF measurements from a bolus-tracking NIRS method that used transient hypoxia as a flow tracer and hypercapnia-induced increases in CBF measured by DCS., Approach: Twelve participants (7 female, 28 ± 6 years) completed a hypercapnia protocol with simultaneous CBF recordings from DCS and arterial spin labeling (ASL). Nine participants completed the transient hypoxia protocol while instrumented with time-resolved NIRS. The estimate of baseline CBF was subsequently used to calibrate hypercapnic DCS data., Results: Moderately strong correlations at baseline ( slope = 0.79 and R 2 = 0.59 ) and during hypercapnia ( slope = 0.90 and R 2 = 0.58 ) were found between CBF values from calibrated DCS and ASL (range 34 to 85    mL / 100    g / min )., Conclusions: Results demonstrated the feasibility of an all-optics approach that can both quantify CBF and perform continuous perfusion monitoring., (© 2024 The Authors.)

Insulin has important vasodilatory effects in the peripheral circulation, but less is known about insulin's role in cerebrovascular control. Herein, we hypothesized both systemic (intravenous) and local (intranasal) insulin administration would increase indices of cerebral blood flow and reduce cerebrovascular compliance (Ci) in young adults. Participants were assigned to one of four separate protocols. Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) and blood pressure (BP, finger photoplethysmography) were measured at baseline and at 1 ) 2 min of carbon dioxide (CO 2 ) air breathing (high flow control), 2 ) 60 min of euglycemic intravenous insulin infusion (40 mU/m 2 body surface area/min), 3 ) 60 min following 160 IU of intranasal insulin, 4 ) 60 minutes of time control. Ci was calculated (modified Windkessel model). Intravenous insulin increased serum insulin (6.0 ± 2.6 to 52.7 ± 12.7 μIU/mL, P < 0.001), whereas serum insulin was reduced following intranasal insulin (6.9 ± 4.5 to 4.9 ± 1.8 μIU/mL, P = 0.030). MCAv increased in response to CO 2 (60 ± 13 to 69 ± 11 cm/s, P < 0.001) but was unchanged with time control (50 ± 7 to 49 ± 8, P = 0.658) and both insulin conditions (intravenous: 61 ± 13 to 62 ± 17 cm/s, P = 0.531; intranasal: 57 ± 12 to 51 ± 15 cm/s; p = 0.061). In contrast, Ci remained at baseline levels over time ( P = 0.438) and was reduced from baseline under CO 2 and both insulin conditions (CO 2 , P < 0.001; intravenous, P = 0.021; intranasal, P = 0.001). Contrary to our hypothesis, there was no effect of systemic or local insulin administration on resting MCAv in young adults; however, both systemic and local insulin administration reduced Ci. These findings advance our understanding of the cerebrovascular response to acute insulin exposure. NEW & NOTEWORTHY Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Contrary to our hypothesis, there was no effect of systemic (intravenous) nor local (intranasal) insulin administration on middle cerebral artery blood velocity; however, both systemic and local insulin administration reduced cerebrovascular compliance. Our findings advance our understanding of the cerebrovascular response to insulin and may have implications in the context of known metabolic disturbances.

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS)., Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery., Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts., Results: In the first protocol ( 28 ± 5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients ( 65 ± 15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed., Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols., (© 2024 The Authors.)

The endothelin-B (ET B ) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ET B receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E 2 ) on ET B receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E 2 exposure modulates ET B receptor-mediated dilation in young women. Fifteen young women (24 ± 4 yr, 24 ± 3 kg/m 2 ) completed the study. Endogenous sex hormone production was suppressed with daily administration of a gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) for 10 days; E 2 (0.1 mg/day, Vivelle-Dot patch) was added back on days 4-10 . We measured vasodilation in the cutaneous microcirculation (microvascular endothelial function) via local heating (42°C) on day 4 (GnRHant) and day 10 (GnRHant + E 2 ) using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer's (control) and ET B receptor antagonist (BQ-788, 300 nM). During GnRHant, vasodilatory responses to local heating were enhanced with ET B receptor blockade (control: 83 ± 9 vs. BQ-788: 90 ± 5%CVC max , P = 0.004). E 2 administration improved vasodilation in the control site (GnRHant: 83 ± 9 vs. GnRHant + E 2 : 89 ± 8%CVC max , P = 0.036). Furthermore, cutaneous vasodilatory responses during ET B receptor blockade were blunted after E 2 administration (control: 89 ± 8 vs. BQ-788: 84 ± 8%CVC max , P = 0.047). These data demonstrate that ovarian hormones, specifically E 2 , modulate ET B receptor function and contribute to the regulation of microvascular endothelial function in young women. NEW & NOTEWORTHY The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.

The endothelin system plays an important role in mediating vascular function. The endothelin-B receptor (ET B R) on endothelial cells mediates vasodilation via nitric oxide production. The vasodilatory effect of the ET B R is lost following menopause and may contribute to impaired vascular endothelial function in postmenopausal women (PMW). However, it is unclear if these functional changes are due to changes in ET B R expression on the endothelium. Therefore, the purpose of this study was to test the hypothesis that endothelial cell ET B R expression is lower in PMW compared with young women (YW). Primary endothelial cells were harvested from the antecubital vein of healthy PMW ( n = 15, 60 ± 6 yr) and YW ( n = 15, 22 ± 2 yr). Cells were identified as endothelial cells by staining for vascular endothelial cadherin, and nuclear integrity was assessed using 4',6-diamidino-2-phenylindole (DAPI). Within those cells, ET B R was quantified using immunocytochemistry; fluorescence intensity was measured in 30 cells and averaged for each participant. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Endothelial cell ET B R expression was lower in PMW [0.46 ± 0.11 arbitrary units (AU)] compared with YW (0.58 ± 0.14 AU; P = 0.02). Furthermore, significant correlations between ET B R expression and FMD ( r = 0.47, P < 0.01), total cholesterol ( r = -0.38, P = 0.04), and LDL cholesterol ( r = -0.39, P = 0.03) were observed. These data demonstrate that endothelial cell ET B R expression is attenuated in PMW. These novel findings provide additional insight into the mechanisms underlying vascular endothelial dysfunction in PMW. NEW & NOTEWORTHY Our study provides novel data demonstrating attenuated endothelial ET B R expression in postmenopausal women. Furthermore, our data extend current knowledge by demonstrating a positive relation between ET B R expression and brachial artery flow-mediated dilation. These findings provide additional mechanistic insight into vascular endothelial dysfunction in postmenopausal women.