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The aim of the current study was to establish the interplay between blood flow patterns within a large cerebral artery and a downstream microvascular segment under conditions of transiently reduced mean arterial pressure (MAP). We report data from nine young, healthy participants (5 women; 26 ± 4 yr) acquired during a 15-s bout of sudden-onset lower body negative pressure (LBNP; -80 mmHg). Simultaneous changes in microvascular cerebral blood flow (CBF) and middle cerebral artery blood velocity (MCAvmean) were captured using diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound (TCD), respectively. Brachial blood pressure (finger photoplethysmography) and TCD waveforms were extracted at baseline and during the nadir blood pressure (BP) response to LBNP and analyzed using a modified Windkessel model to calculate indices of cerebrovascular resistance (Ri) and compliance (Ci). Compared with baseline, rapid-onset LBNP decreased MAP by 22 ± 16% and Ri by 14 ± 10% (both P ≤ 0.03). Ci increased (322 ± 298%; P < 0.01) but MCAvmean (-8 ± 16%; P = 0.09) and CBF (-2 ± 3%; P = 0.29) were preserved. The results provide evidence that changes in both vascular resistance and compliance preserve CBF, as indexed by no significant changes in MCAvmean or DCS microvascular flow, during transient hypotension. [ABSTRACT FROM AUTHOR]

Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are frequently used during vascular and cardiac surgeries as a non-invasive means of assessing brain health; however, signal contamination from extracerebral tissues remains a concern. As an alternative, hyperspectral (hs)NIRS can be used to measure changes in the oxidation state of cytochrome c oxidase (ΔoxCCO), which provides greater sensitivity to the brain given its higher mitochondrial concentration versus the scalp. The purpose of this study was to evaluate the depth sensitivity of the oxCCO signal to changes occurring in the brain and extracerebral tissue components. The oxCCO assessment was conducted using multi-distance hsNIRS (source-detector separations = 1 and 3 cm), and metabolic changes were compared to changes in StO2. Ten participants were monitored using an in-house system combining hsNIRS and diffuse correlation spectroscopy (DCS). Data were acquired during carotid compression (CC) to reduce blood flow and hypercapnia to increase flow. Reducing blood flow by CC resulted in a significant decrease in oxCCO measured at rSD = 3 cm but not at 1 cm. In contrast, significant changes in StO2 were found at both distances. Hypercapnia caused significant increases in StO2 and oxCCO at rSD = 3 cm, but not at 1 cm. Extracerebral contamination resulted in elevated StO2 but not oxCCO after hypercapnia, which was significantly reduced by applying regression analysis. This study demonstrated that oxCCO was less sensitive to extracerebral signals than StO2. [ABSTRACT FROM AUTHOR]

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]

The endothelin system plays an important role in mediating vascular function. The endothelin-B receptor (ETBR) on endothelial cells mediates vasodilation via nitric oxide production. The vasodilatory effect of the ETBR 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 ETBR expression on the endothelium. Therefore, the purpose of this study was to test the hypothesis that endothelial cell ETBR 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, ETBR 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 ETBR 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 ETBR 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 ETBR 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 ETBR expression in postmenopausal women. Furthermore, our data extend current knowledge by demonstrating a positive relation between ETBR expression and brachial artery flow-mediated dilation. These findings provide additional mechanistic insight into vascular endothelial dysfunction in postmenopausal women. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of the study?What are the effects of acute mental stress on the mechanisms regulating cerebral blood flow?What is the main finding and its importance?The major new findings are as follows: (i) high mental stress and hypercapnia had an interactive effect on mean middle cerebral artery blood velocity; (ii) high mental stress altered the regulation of cerebral blood flow; (iii) the increased cerebrovascular hypercapnic reactivity was not driven by changes in mean arterial pressure alone; and (iv) this increased perfusion with mental stress appeared not to be justified functionally by an increase in oxygen demand (as determined by near‐infrared spectroscopy‐derived measures). In this study, we examined the effects of acute mental stress on cerebrovascular function. Sixteen participants (aged 23 ± 4 years; five female) were exposed to low and high mental stress using simple arithmetic (counting backwards from 1000) and more complex arithmetic (serial subtraction of 13 from a rapidly changing four‐digit number), respectively. During consecutive conditions of baseline, low stress and high stress, end‐tidal partial pressure of CO2 (P ET ,CO2) was recorded at normocapnia (37 ± 3 mmHg) and clamped at two elevated levels (P < 0.01): 41 ± 1 and 46 ± 1 mmHg. Mean right middle cerebral artery blood velocity (MCAvmean; transcranial Doppler ultrasound), right prefrontal cortex haemodynamics (near‐infrared spectroscopy) and mean arterial blood pressure (MAP; finger photoplethysmography) were measured continuously. Cerebrovascular hypercapnic reactivity (ΔMCAvmean/ΔP ET ,CO2), cerebrovascular conductance (CVC; MCAvmean/MAP), CVC CO2 reactivity (ΔCVC/ΔP ET ,CO2) and total peripheral resistance (MAP/cardiac output) were calculated. Acute high mental stress increased MCAvmean by 7 ± 7%, and more so at higher P ET ,CO2 (32 ± 10%; interaction, P = 0.03), illustrating increased sensitivity to CO2 (i.e. its major regulator). High mental stress also increased MAP (17 ± 9%; P ≤ 0.01), coinciding with increased near‐infrared spectroscopy‐derived prefrontal haemoglobin volume and saturation measures. High mental stress elevated both cerebrovascular hypercapnic and conductance reactivities (main effect of stress, P ≤ 0.04). These findings indicate that the cerebrovascular response to acute high mental stress results in a coordinated regulation between multiple processes. [ABSTRACT FROM AUTHOR]

This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10± 2; P < 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (HbSat: 56 13 vs. 71 6%; P 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P < 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also thewithin-burst axonal recruitment normally observed during progressive chemoreflex stress. [ABSTRACT FROM AUTHOR]

R6155 --> 757.39 --> The cutaneous microvasculature is considered a representative vascular bed and is regularly used to interrogate the mechanisms of microvascular function in healthy and diseased humans. For instance, cutaneous dilation in response to local heating can provide an index of nitric oxide (NO) bioavailability. While the skin of the forearm is typically used for local heating studies, some studies have used the ventral forearm while others have used the dorsal forearm skin for this assessment. Since the dorsal aspect of the forearm typically has more hair and receives greater sun exposure than the ventral side, there is speculation that cutaneous dilation may differ from one side of the forearm to the other, in magnitude and/or mechanism. As such, studies utilizing different sides of the forearm may not be comparable. Therefore, we aimed to test the hypothesis that cutaneous local heating responses differ between the ventral and dorsal aspects of the forearm in response to the two most common temperature stimuli, 39°C and 42°C. Methods: Ten young, normotensive individuals (6 men/4 women, age: 26 ± 2 years) were studied on two separate occasions separated by 2‐7 days. At each visit, 4 intradermal microdialysis fibers were placed in either the ventral or dorsal forearm, in a random order. Two fibers were perfused with Ringer's solution to serve as control sites and the other 2 fibers were perfused with 10 mM N(G)‐Nitro‐L‐arginine methyl ester (L‐NAME) to inhibit NO synthase. Red blood cell flux (RBCF) was assessed at all sites via laser Doppler flowmetry. Each pair of sites (control and L‐NAME) was heated to either 39°C or 42°C for ~40‐45 min until RBCF plateaued. All sites were then infused with 28 mM sodium nitroprusside and heated to 43°C to establish maximal RBCF. Cutaneous vascular conductance (CVC) was calculated as RBCF / mean arterial pressure measured during the plateau and maximal phases. Plateau results are reported as a percentage of maximal CVC at each respective site. The relative NO contribution is reported as: [(control plateau – L‐NAME plateau)/control plateau] x 100. Results: No differences were observed at the control site between ventral and dorsal aspects of the forearm when heated to 39°C (62 ± 13 vs. 62 ± 16 % CVCmax, P=0.99). Likewise, the heating response to 42°C was similar across the forearm (ventral: 90 ± 9 vs. dorsal: 86 ± 12% CVCmax, P=0.21). The relative contribution of NO to the plateau was comparable across the forearm at 39°C (ventral: 70 ± 20 vs. dorsal: 66 ± 21%, P=0.71) and 42°C (ventral: 63 ± 16 vs. dorsal: 69 ± 11%, P=0.11). Discussion: These preliminary findings suggest that cutaneous vasodilation elicited by local heating is similar on both sides of the forearm at both 39°C and 42 °C. Additionally, it appears that the relative contribution of NO to local heating‐induced microvascular vasodilation is not different across the forearm. [ABSTRACT FROM AUTHOR]

Fine-tuning our understanding of the baroreflex: size-dependent regulation of action potential subpopulations Keywords: action potential; baroreflex; lower body negative pressure; muscle sympathetic nerve activity EN action potential baroreflex lower body negative pressure muscle sympathetic nerve activity 2291 2292 2 06/16/20 20200615 NES 200615 The sympathetic arm of the arterial baroreflex is a homeostatic mechanism which rapidly regulates blood pressure (BP) via changes in sympathetic outflow. These APs can be extracted from a multi-unit MSNA recording using a wavelet de-noising approach based on the principle that each axon produces a characteristic AP morphology (Salmanpour I et al i . [Extracted from the article]

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.)

Significance: Hyperspectral near-infrared spectroscopy (hsNIRS) combined with diffuse correlation spectroscopy (DCS) provides a noninvasive approach for monitoring cerebral blood flow (CBF), the cerebral metabolic rate of oxygen ( CMRO 2 ) and the oxidation state of cytochrome-c-oxidase (oxCCO). CMRO 2 is calculated by combining tissue oxygen saturation ( S t O 2 ) with CBF, whereas oxCCO can be measured directly by hsNIRS. Although both reflect oxygen metabolism, a direct comparison has yet to be studied. Aim: We aim to investigate the relationship between CMRO 2 and oxCCO during periods of restricted oxygen delivery and lower metabolic demand. Approach: A hybrid hsNIRS/DCS system was used to measure hemodynamic and metabolic responses in piglets exposed to cerebral ischemia and anesthetic-induced reductions in brain activity. Results: Although a linear relationship was observed between CMRO 2 and oxCCO during ischemia, both exhibited a nonlinear relationship with respect to CBF. In contrast, linear correlation was sufficient to characterize the relationships between CMRO 2 and CBF and between the two metabolic markers during reduced metabolic demand. Conclusions: The observed relationship between CMRO 2 and oxCCO during periods of restricted oxygen delivery and lower metabolic demand indicates that the two metabolic markers are strongly correlated., (© 2022 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.