American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Sudorific agonist pathways: Which direction to take and are there possible interactions?","authors":"Thad E Wilson, Kristen Metzler-Wilson, Kelsey A Bullens","doi":"10.1152/ajpregu.00041.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00041.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmented analgesic effect of tyramine or octopamine in combination with lidocaine is mediated with α-adrenergic receptors.","authors":"An-Kuo Chou, Chong-Chi Chiu, Yu-Wen Chen, Ching-Hsia Hung, Jhi-Joung Wang","doi":"10.1152/ajpregu.00225.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00225.2024","url":null,"abstract":"<p><p>Although norepinephrine is known to enhance the antinociceptive effect of the local anesthetic lidocaine, the effects of two precursors of norepinephrine, tyramine and octopamine, on the antinociceptive potency of lidocaine are not known. We aimed to investigate cutaneous antinociceptive interactions and mechanism of action of tyramine and octopamine, and their respective co-injections with lidocaine, in comparison with norepinephrine. Cutaneous nociceptive blockade in rats was quantified by the blockage of cutaneous trunci muscle reflexes induced by needle pinpricks. Isobolographic analysis was employed to estimate the interactions between lidocaine and drugs (tyramine, octopamine, or norepinephrine). Phentolamine was added to a two-drug combination. At ED₇₅ (75% effective dose), subcutaneous injection of tyramine and lidocaine provoked 73% and 77% nociceptive blockade. After isobolographic analysis, the theoretical ED₅₀ was significantly greater than the experimental ED₅₀ in both octopamine-lidocaine combination and norepinephrine-lidocaine combination (<i>p</i><0.01), but not in tyramine-lidocaine combination. Lidocaine (ED₉₅) in combination with tyramine (30 μmole), octopamine (12 μmole), or norepinephrine (0.007 μmole) prolonged the duration of nociceptive blockade (<i>p</i><0.05). The addition of phentolamine (0.06 μmole) to a combination of tyramine (30 μmole) and lidocaine (ED₉₅), a combination of octopamine (12 μmole) and lidocaine (ED₉₅), or a combination of n orepinephrine (0.007 μmole) and lidocaine (ED₉₅) showed a nociceptive blocking effect similar to that of lidocaine (ED₉₅) alone. Tyramine and octopamine presented dose-dependent cutaneous nociceptive blockades. Tyramine-lidocaine combination produced an additive effect. The combination of octopamine-lidocaine and norepinephrine-lidocaine showed synergistic effects that was inhibited by phentolamine, suggesting that this synergistic effect is mediated with alpha-adrenergic receptors.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of an exercise- and passive-induced heat stress on autophagy in young and older males.","authors":"James J McCormick, Kelli E King, Nicholas Goulet, Andres E Carrillo, Naoto Fujii, Tatsuro Amano, Pierre Boulay, Glen P Kenny","doi":"10.1152/ajpregu.00232.2024","DOIUrl":"10.1152/ajpregu.00232.2024","url":null,"abstract":"<p><p>Although activation of autophagy is vital for cellular survival during exposure to ambient heat and exercise, it remains unclear if autophagic activity differs between these heat stress conditions and if aging mediates this response. Young [<i>n</i> = 10, mean (SD): 22 (2) yr] and older males [<i>n</i> = 10, 70 (5) yr] performed 30 min of semi-recumbent cycling (70% maximal oxygen uptake). On a separate day, participants were immersed in warm water for 30 min, with the water temperature adjusted to induce the same increase in core temperature (rectal) as the prior exercise bout. Proteins associated with autophagy, inflammation, apoptosis, and the heat shock response (HSR) were assessed in peripheral blood mononuclear cells via Western blot before and after each exposure and during a 6-h seated recovery in a temperate environment (∼22°C). No differences in core temperature occurred at end-exposure to exercise or passive heating in either group (both, <i>P</i> ≥ 0.999). Older adults exhibited greater autophagic regulation (significant LC3-II accumulation) to exercise when compared with passive heating at all time points (all, <i>P</i> ≤ 0.022). However, passive heating alone may have impaired autophagy (elevated p62; <i>P</i> = 0.044). Pro-inflammatory IL-6 was elevated during both conditions (<i>P</i> < 0.001) in older adults. Conversely, greater autophagic initiation (i.e., beclin-2) occurred in young adults at end-exercise and 3-h recovery when compared with passive heating (both, <i>P</i> ≤ 0.024). The HSR and apoptotic responses were similar between conditions in both groups. Although brief exercise stimulates autophagy, exposure to ambient heat stress of an equivalent heat load may underlie autophagic dysregulation in older adults.<b>NEW & NOTEWORTHY</b> We show that a short-duration (30-min) bout of vigorous-intensity exercise stimulates autophagy in young and older males when performed in a temperate environment. However, when exposed to an equivalent heat load as achieved during the prior exercise bout to elicit the same relative increase in core temperature via warm-water immersion, autophagic dysregulation occurs in older but not younger males.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R289-R299"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Submandibular gland removal decreases avoidance of bitter taste in mice.","authors":"Masataka Narukawa, Yukino Matsuhara, Remi Umano, Momo Murata, Ippei Watari, Takashi Ono, Takumi Misaka","doi":"10.1152/ajpregu.00290.2024","DOIUrl":"10.1152/ajpregu.00290.2024","url":null,"abstract":"<p><p>Saliva plays a crucial role in digestion, including taste perception, food breakdown, chewing, swallowing, and bolus formation. Saliva is mainly produced by three pairs of major glands: parotid, submandibular, and sublingual glands. To evaluate the effect of each salivary gland on taste preference, we conducted a 48-h two-bottle preference test using mouse models in which the parotid glands (PGs), submandibular glands (SMGs), or sublingual glands (SLGs) were surgically removed. The taste preferences for the five basic tastes of the PG- and SLG-removed mice were similar to those of the control mice. However, in SMG-removed mice, the avoidance of bitter compounds was significantly decreased. These findings indicate that the SMG plays an important role in bitter taste perception among the three major salivary glands. To investigate the reasons for this preference change, we examined the impact of salivary gland removal on the expression of taste-related molecules in the taste buds. No apparent changes were observed in the expression of these molecules after salivary gland removal. When comparing the protein concentration and composition of saliva between the control and salivary gland removal groups, we found that, although the protein concentration did not change significantly, its composition was substantially altered by SMG removal. These results suggest that changes in protein composition in saliva may be one of the factors responsible for the altered bitter preferences observed in the SMG-removed mice.<b>NEW & NOTEWORTHY</b> Using mouse models with surgically removed parotid glands (PGs), submandibular glands (SMGs), or sublingual glands (SLGs), we examined taste preferences. PG- and SLG-removed mice showed no significant changes in preference, but SMG removal notably reduced the avoidance of bitter compounds. Although the salivary protein concentration remained unchanged, its composition was altered by SMG removal, suggesting that these changes may underlie the modified perception of bitter taste.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R300-R305"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral contraceptive pill phase alters mechanisms contributing to cutaneous microvascular function in response to local heating.","authors":"Casey G Turner, Anna E Stanhewicz, Karen E Nielsen, Jeffrey S Otis, Rafaela G Feresin, Brett J Wong","doi":"10.1152/ajpregu.00159.2024","DOIUrl":"10.1152/ajpregu.00159.2024","url":null,"abstract":"<p><p>The purpose of this study was to investigate the effect of oral contraceptive pill (OCP) phase on in vivo microvascular endothelium-dependent vasodilation and contributions of nitric oxide (NO), cyclooxygenase (COX), and endothelial-derived hyperpolarizing factors (EDHFs). Participants completed two experimental visits in random order, during the <i>1</i>) low and <i>2</i>) high hormone phase of the OCP cycle. Endothelium-dependent dilation was assessed in the cutaneous microvasculature via local heating at four intradermal microdialysis sites treated with: <i>1</i>) lactated Ringer's (control), <i>2</i>) 10 mM ketorolac (Keto, COX inhibitor), <i>3</i>) 50 mM tetraethylammonium (TEA, calcium-activated potassium channel inhibitor), and <i>4</i>) 10 mM ketorolac + 50 mM TEA (Keto + TEA). Perfusion of 20 mM <i>N</i>^ω-nitro-l-arginine methyl ester (l-NAME) at each site was used to quantify the l-NAME-sensitive component of dilation, suggesting NO contribution. There was no effect of OCP phase on endothelium-dependent dilation (<i>P</i> = 0.75) or the l-NAME-sensitive component of the response (<i>P</i> = 0.09, <i>d</i> = 0.7) at control sites. Inhibition of COX increased baseline blood flow regardless of OCP phase (all <i>P</i> < 0.01). Control and Keto sites elicited greater endothelium-dependent dilation than TEA and Keto + TEA sites in both phases (all <i>P</i> < 0.0001). During the low hormone phase, the l-NAME-sensitive component was greater at control compared with TEA sites (<i>P</i> < 0.01). During the high hormone phase, the l-NAME-sensitive component was greater at Keto compared with TEA sites (<i>P</i> < 0.01). Within-participant differences between control and Keto sites support a phase-dependent restraint of NO activity via COX pathways (<i>P</i> = 0.01). These findings demonstrate that the OCP phase affects underlying mechanistic pathways contributing to cutaneous microvascular endothelial function.<b>NEW & NOTEWORTHY</b> This study investigates the effect of OCP phase on in vivo microvascular endothelium-dependent vasodilation and explores underlying mechanisms. Present findings suggest OCP phase does not affect overall microvascular endothelium-dependent dilation but does affect the underlying mechanisms. In women using OCP, there is a robust reliance on EDHF pathways and the COX pathway moderates basal microvascular blood flow and demonstrates a phase-dependent restraint of the NO pathway.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R374-R385"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the central and peripheral omega 3 oxylipin response to acute systemic inflammation.","authors":"Julia C Kelliher, Ivana Maric, Christopher G Engeland, Gregory C Shearer, Karolina P Skibicka","doi":"10.1152/ajpregu.00242.2024","DOIUrl":"10.1152/ajpregu.00242.2024","url":null,"abstract":"<p><p>High-density lipoprotein (HDL) oxylipins regulate inflammation, and acute systemic inflammation can precipitate cognitive impairment. Females have more HDL and stronger immune responses than males, yet higher dementia risk. Little is known about sex differences in oxylipin responses to inflammatory stimuli and potential crosstalk between acute systemic inflammation and central oxylipin signaling in either sex. In this targeted lipidomics study, we used liquid chromatography with tandem mass spectrometry (LC/MS/MS) to characterize oxylipin profiles in plasma HDL and cerebrospinal fluid (CSF) of male and female rats following an intraperitoneal interleukin-1β (IL-1β)-induced inflammatory challenge to determine whether and how peripheral and central oxylipins respond to acute systemic inflammation in both sexes. We hypothesized that females mount a greater oxylipin response to IL-1β than males and that acute activation of peripheral inflammatory pathways changes central oxylipin concentrations. We found that IL-1β altered the abundance of omega (ω)6 and ω3 oxylipins in plasma HDL and CSF of both sexes. However, IL-1β reduced global concentrations of peripheral and central oxylipins in plasma HDL and CSF, respectively, in female rats only. Reduced oxylipin concentrations in IL-1β-treated females were driven by a loss of anti-inflammatory ω3 eicosapentaenoic acid (EPA)-derived dihydroxyeicosatetraenoic acids (DiHETEs) in plasma HDL and CSF. Interestingly, plasma HDL and CSF concentrations of EPA-derived DiHETEs were only correlated in IL-1β-treated rats, suggesting increased periphery-brain crosstalk during acute systemic inflammation. Overall, the sexually dimorphic responses of peripheral and central oxylipins to acute systemic inflammation provide molecular insight into sex differences in both innate immunity and neuroinflammatory responses.<b>NEW & NOTEWORTHY</b> This study examines previously unexplored sex differences in oxylipin signaling cascade activation in the central nervous system and periphery during the acute phase response. This is the first study to assess and correlate oxylipins in plasma HDL and CSF in males and females following an acute systemic inflammatory challenge. This work showing reduced concentrations of anti-inflammatory ω3 EPA-derived DiHETEs in acutely inflamed females provides molecular insight into sex differences in immunity and inflammation-induced neurological changes.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R341-R351"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The catecholamine response to graded high-altitude flight in yellow-rumped warblers (<i>Setophaga coronata</i>).","authors":"Catherine M Ivy, Kevin G Young, Melanie Qu, Morag F Dick, J Kevin Shoemaker, Christopher G Guglielmo","doi":"10.1152/ajpregu.00197.2024","DOIUrl":"10.1152/ajpregu.00197.2024","url":null,"abstract":"<p><p>Chronic exposure to low oxygen (hypoxia) leads to amplification of the hypoxic chemoreflex, increasing breathing and sympathetic nervous system (SNS) activation. Prolonged SNS activation redistributes blood to hypoxia-sensitive tissues away from muscles. Recent tracking studies have shown that migratory songbirds can fly 5,000 m or higher above sea level, leading us to hypothesize that migratory birds may have a blunted hypoxic chemoreflex to maintain blood flow to muscles during migratory flight at high altitudes. To test this hypothesis, we used a hypobaric wind tunnel and measured circulating plasma catecholamines after maximal altitude flight, flight at 75% of maximal altitude, flight at ground level (∼250 m), and after rest at 75% of maximal altitude and ground level in migratory myrtle yellow-rumped warblers (<i>Setophaga coronata</i>). Yellow-rumped warblers were capable of flying above 4,000 m simulated altitude above sea level (average maximum altitude of ∼3,600 m) and would maintain flights at 75% of individual maximum altitudes (∼2,700 m). Circulating dopamine and noradrenaline were similar between resting and flight conditions at ground level and with exposure to 75% of maximal altitude, whereas adrenaline significantly increased with flight, but did not change further with flight at 75% of maximal altitude. In contrast, both adrenaline and noradrenaline concentrations increased after maximum altitude flights compared with 75% and ground-level flights. Our findings show that exercise increases plasma adrenaline in migratory songbirds and suggest that warblers flying at high altitudes below their maximum altitude may be minimally hypoxic, allowing them to maintain oxygen transport to flight muscles.<b>NEW & NOTEWORTHY</b> Yellow-rumped warblers, a small songbird that conducts migratory flights, were found to fly to altitudes above 4,000 m above sea level in simulated flights using a hypobaric wind tunnel. Circulating adrenaline suggests that warblers flying at 75% of individual maximum altitudes are not experiencing arterial hypoxia, allowing them to maintain aerobically demanding migratory flight at high altitudes.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R329-R340"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multisystem impact of altering acid load of ingested exogenous ketone supplements at rest in young healthy adults.","authors":"Tyler S McClure, Jeffrey D Buxton, Brendan Egan, Emma Plank, Makenna Isles, Dana L Ault, Philip J Prins, Andrew P Koutnik","doi":"10.1152/ajpregu.00057.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00057.2024","url":null,"abstract":"<p><p>Disruptions to acid-base are observed in extreme environments as well as respiratory and metabolic diseases. Exogenous ketone supplements (EKSs) have been proposed to mitigate these processes and provide therapeutic benefits by altering acid-base balance and metabolism, but direct comparison of various forms of EKS is lacking. Twenty healthy participants (M/F: 10/10; age: 20.6 ± 2.0 yr, height: 1.72 ± 0.08 m, body mass: 67.9 ± 10.2 kg) participated in a single-blind, randomized crossover design comparing ingestion of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME), KME + sodium bicarbonate (KME + BIC), an R-βHB ketone salt (KS), and a flavor-matched placebo. Acid-base balance, blood R-βHB, glucose and lactate concentrations, blood gases, respiratory gas exchange, autonomic function, and cognitive performance were assessed at baseline and various timepoints for up to 120 min after ingestion. Compared with placebo (PLA), blood R-βHB concentrations were elevated in each EKS condition (∼2-4 mM; <i>P</i> < 0.01), and blood glucose concentrations were lower. Blood pH was lower in KME (-0.07 units), and higher in KS and KME + BIC (+0.05 units), compared with PLA (all <i>P</i> < 0.05). Heart rate was elevated, and autonomic function was altered in KME + BIC. There were no differences between conditions for blood gases, respiratory gas exchange, blood pressure, or cognitive performance. Exploratory analyses of between-sex differences demonstrated males and females responded similarly across all outcome measures. Altering the acid load of EKS modulated the response of blood R-βHB and glucose concentrations but had only modest effects on other outcome measures at rest in young healthy adults, with no differences observed between sexes.<b>NEW & NOTEWORTHY</b> Altering the acid load of ingested exogenous ketone supplements altered post-ingestion responses of circulating glucose and R-βHB concentrations, heart rate, and autonomic function, but did not alter blood gases, respiratory gas exchange, blood pressure, or cognitive performance at rest in young healthy adults.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"328 3","pages":"R386-R395"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estradiol levels are differentially associated with pulse wave velocity in trauma-exposed premenopausal women with and without PTSD.","authors":"Chasity Corbin, Chowdhury Ibtida Tahmin, Chowdhury Tasnova Tahsin, Zynab Ahmed, Redeat Wattero, Azhaar Mohamed, Susan B Racette, Daniel Duprez, Ida T Fonkoue","doi":"10.1152/ajpregu.00262.2024","DOIUrl":"10.1152/ajpregu.00262.2024","url":null,"abstract":"<p><p>Arterial stiffness is a well-known risk factor for cardiovascular disease. Although estradiol (E2) is known to be cardioprotective, the available data point to a growing cardiovascular disease risk in women before menopause due to posttraumatic stress disorder (PTSD). The present study aimed to investigate the effects of E2 on arterial compliance in trauma-exposed premenopausal women, with and without a clinical diagnosis of PTSD. We hypothesized that E2 will be differentially associated with pulse wave velocity (PWV) in women with PTSD (PTSD⁺, <i>n</i> = 45) and without PTSD (PTSD^-, <i>n</i> = 47). Estradiol and PWV were measured during two separate study visits. Serum E2 levels were measured via the quantitative sandwich enzyme-linked immunoassay technique (ELISA) and log-transformed due to non-normal distribution. Carotid to femoral applanation tonometry was used to measure PWV. Our analyses revealed an overall weak and nonsignificant correlation between E2 and PWV (<i>r</i> = -0.119, <i>P</i> = 0.350). However, when examining each group, we found a negative association between E2 and PWV in PTSD^- (<i>r</i> = -0.466, <i>P</i> = 0.004). In contrast, we found an unexpected positive association between E2 levels and PWV in PTSD⁺ (<i>r</i> = 0.360, <i>P</i> = 0.037). Furthermore, a multiple linear regression revealed that E2 was predictive of PWV in PTSD^- only, even after accounting for the phase of the menstrual cycle, age, body mass index, diastolic blood pressure, and PTSD symptom severity (<i>R</i>² = 0.670, <i>P</i> = 0.005). Interestingly, we also found lower levels of E2 in PTSD⁺ than PTSD^- (1.4 ± 0.4 vs. 1.6 ± 0.4 pg/mL, <i>P</i> = 0.022). These findings suggest that PTSD may inhibit the protective effects of E2 on arterial compliance in women before menopause.<b>NEW & NOTEWORTHY</b> In trauma-exposed premenopausal women, we found that serum estradiol (E2) was a predictor of pulse wave velocity (PWV) only in the absence of a posttraumatic stress disorder (PTSD) diagnosis, even after accounting for the phase of the menstrual cycle, age, body mass index, diastolic blood pressure, and PTSD symptom severity. Moreover, E2 levels were lower in women with PTSD than in those without PTSD. We collected E2 and PWV during two separate visits and controlled for the menstrual cycle phase in our analyses.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R235-R241"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of α1 adrenergic receptors in the cerebral cortical blood flow response to acute hypoxia in low- and high-altitude near-term fetal lambs.","authors":"Jacqueline Bierwirth, John B Tan, Bobby D Mendez Padilla, Lubo Zhang, Hobe Schroeder, Taiming Liu, Gordon G Power, Arlin B Blood","doi":"10.1152/ajpregu.00044.2024","DOIUrl":"10.1152/ajpregu.00044.2024","url":null,"abstract":"<p><p>Fetal cerebral blood flow increases in response to acute hypoxia, mediated in part by an adrenergic α₁ receptor (α₁-R)-mediated increase in peripheral vascular resistance that redirects cardiac output to the brain. Activation of cerebral α₁-R may attenuate the increase in cerebral blood flow during hypoxia, and this effect may be even greater in fetuses exposed to chronic high-altitude hypoxia, which has previously been shown to increase the contractile function of cerebral artery α₁-Rs. We hypothesized that α₁-R activation in the fetal sheep brain attenuates increases in cerebral blood flow during acute hypoxia and that this effect would be accentuated in fetuses exposed to chronic hypoxia. Near-term fetal sheep gestated at low or high altitudes (3,801 m) were instrumented chronically for measurement of mean arterial pressure (MAP), heart rate, cerebral cortical blood flow (CBF), and cortical vascular resistance (CVR). Responses to acute hypoxia were then measured in the presence and absence of prazosin (α₁-R antagonist). Prazosin infusion resulted in a decrease in baseline MAP and CBF. During acute hypoxia, CBF increased by only 14 ± 6% above baseline in the prazosin group, compared with 28 ± 9% in the vehicle group with no significant difference in CVR in either group. Similar to the low-altitude animals, prazosin did not significantly alter the CBF or CVR response to acute hypoxia, nor recovery following acute hypoxia, in the high-altitude fetuses. We conclude that cortical α₁-Rs neither attenuate increased CBF during acute hypoxia nor mediate the cortical vasoconstriction that occurs in recovery from acute hypoxia.<b>NEW & NOTEWORTHY</b> The results of this study indicate that α1-adrenergic receptors on the cerebral vasculature do not mediate cerebral vasoconstriction during acute hypoxic stress, despite a known increase in circulating catecholamine concentrations and sympathetic tone. The same is true for fetuses exposed to chronic hypoxia, which is known to increase the vasocontractile activity of α1-receptors.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R364-R373"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}