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

{"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":"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":"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}

{"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167166/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"True or false: arterial stiffening in the seated position.","authors":"Amane Hori, Masaki Mizuno","doi":"10.1152/ajpregu.00008.2025","DOIUrl":"10.1152/ajpregu.00008.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R287-R288"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063151","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 atrial natriuretic peptide and oxytocin in gastric emptying delay induced by right atrial stretch in rats.","authors":"Raimundo C Palheta, Moisés T B da Silva, Ana Débora N P Georgii, Camila M S Silva, Rômmulo C L Siqueira, Wagner L Reis, Silvia G Ruginsk, Lucila L K Elias, José Antunes-Rodrigues, Armênio A Santos","doi":"10.1152/ajpregu.00172.2024","DOIUrl":"10.1152/ajpregu.00172.2024","url":null,"abstract":"<p><p>Fluid volume and osmolality balance are maintained by complex neuroendocrine and liquid-salt intake behavior, cardiovascular and renal mechanisms, and gastrointestinal adjustments. Mechanical stretching of the right atrium [atrial stretch (AS)] enhances central venous pressure and heart rate while decreasing gastric emptying (GE) of liquid in rats. We evaluated the effect of AS on GE and plasma levels of atrial natriuretic peptide (ANP), oxytocin (OT), and corticosterone (CORT) to determine whether ANP contributes to the OT-mediated GE delay of liquids due to AS in awake rats. Initially, we performed thoracotomy followed by right appendectomy (AX) or sham thoracotomy. One week later, rats were randomly subjected to pretreatment with NaCl 0.15 M (control), atosiban (AT, OT-antagonist), anantin (ANT, ANP-antagonist), or dexamethasone (DEX). Afterward, 50 µL of AS was administered for 5 min or not (sham). Then, the rats were fed a test meal, and GE of liquids or solids was performed. The other animals were pretreated with NaCl 0.15 M, atosiban, anantin, or dexamethasone, followed by OT treatment for GE assessment. Compared with the sham group, 50 µL of AS decreased the GE of the liquid and solid test meals. This phenomenon was prevented by AT, ANT, DEX, and surgical procedures with AX. AS also increased plasma levels of ANP, OT, and CORT. In turn, oxytocin treatment decreased GE and increased plasma ANP, OT, and CORT levels, while AT, ANT, and DEX prevented OT-induced GE delay. Hence, AS delayed GE of liquid in rats, a phenomenon that involves oxytocinergic pathways and ANP activities.<b>NEW & NOTEWORTHY</b> We suggest a cardiogastric reflex with the participation of neuroendocrine mediators, which contributes to regulating liquid balance in the animal's body. Atrial natriuretic peptide and oxytocin are substances recognized for participating in diuresis and regulating the transit of liquids in the gastrointestinal tract in situations of cardiac volume overload, as was simulated with atrial stretching in the present experimental model.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R396-R407"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405184","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":"Catecholamine synthesis and secretion by adrenal chromaffin cells are reduced in deer mice native to high altitude.","authors":"Nicole A Pranckevicius, Angela L Scott, Aedan J Rourke, Ranim Saleem, Oliver H Wearing, Graham R Scott","doi":"10.1152/ajpregu.00194.2024","DOIUrl":"10.1152/ajpregu.00194.2024","url":null,"abstract":"<p><p>Hypoxia at high altitude can constrain aerobic metabolism and elicit physiological responses that are detrimental to health and fitness. Responses of the sympathoadrenal system are vital for coping with acute hypoxia but can become maladaptive with prolonged activation in chronic hypoxia. We examined how adrenal function is altered in high-altitude populations of deer mice (<i>Peromyscus maniculatus</i>), which have evolved to overcome chronic hypoxia in their native environment. High- and low-altitude populations were each born and raised in common laboratory conditions and then acclimated to normoxia or chronic hypoxia during adulthood. High-altitude mice exhibited lower plasma epinephrine concentrations than low-altitude mice in both normoxia and hypoxia. Primary cultures of chromaffin cells were used to examine the cellular mechanisms underlying differences in epinephrine secretion from the adrenal medulla. Chromaffin cells from high-altitude mice did not mount a diminished Ca²⁺ response to nicotinic stimulation, but cellular catecholamine stores were much lower in high-altitude mice than in low-altitude mice. Histological analyses of the adrenal gland showed that high-altitude mice did not have smaller adrenal medullae. Therefore, reductions in chromaffin cell catecholamine stores were the primary mechanism for lower secretion rates and circulating concentrations of catecholamines in high-altitude mice, which may help avoid sympathoadrenal overactivity in chronic hypoxia. Further exploratory analysis found that high-altitude mice have a larger adrenal cortex and higher plasma concentrations of corticosterone, which could reflect changes in stress responsiveness or metabolic regulation. Therefore, multiple evolved changes in the physiology of the adrenal gland may contribute to high-altitude adaptation in deer mice.<b>NEW & NOTEWORTHY</b> Prolonged activation of the sympathoadrenal system can become maladaptive in chronic hypoxia, but few previous studies have examined adrenal function in high-altitude natives. Comparing high-altitude versus low-altitude populations of mice, we show that high-altitude mice synthesize and store fewer catecholamines in adrenal chromaffin cells and thus have lower secretion rates and circulating concentrations of catecholamines in hypoxia.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R274-R286"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063145","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":"TRPA1 channels modulate cutaneous vasodilation during exercise in the heat in young adults when NOS is inhibited.","authors":"Rei Hattori, Masanobu Kajiki, Tomomi Fujimoto, Tatsuro Amano, Glen P Kenny, Koichi Watanabe, Takeshi Nishiyasu, Naoto Fujii","doi":"10.1152/ajpregu.00269.2024","DOIUrl":"10.1152/ajpregu.00269.2024","url":null,"abstract":"<p><p>Nitric oxide synthase (NOS) is an important mediator of cutaneous vasodilation during exercise-heat stress. We recently reported that pharmacological activation of transient receptor potential ankyrin 1 (TRPA1) channel mediates cutaneous vasodilation via NOS-dependent mechanisms under nonheat stress-resting conditions. Here, we hypothesized that TRPA1 channel activation would contribute to cutaneous vasodilation during exercise in the heat via NOS-dependent mechanisms. To assess this response, we first conducted TRPA1 channel antagonist verification substudy (10 young adults and 5 women) wherein 1 mM ASP7663 (TRPA1 channel agonist) increased cutaneous vascular conductance (CVC; cutaneous blood flow divided by mean arterial pressure) and this response was blocked by ∼50% with 100 μM HC030031, a known TRPA1 channel antagonist. Subsequently, 12 young adults (5 women) completed two bouts of 30-min moderate-intensity cycling (45% of their predetermined peak oxygen uptake) in the heat (35°C). During the first exercise, CVC was evaluated at four dorsal forearm skin sites perfused with a 5% DMSO, whereas in the second bout, all sites were treated with either <i>1</i>) a 5% DMSO (control), <i>2</i>) 100 µM HC030031, <i>3</i>) 20 mM l-NAME, a nonselective NOS inhibitor, or <i>4</i>) combination of both. No between-site differences in CVC were measured during the first exercise (<i>P</i> > 0.182). During the second exercise, HC030031 alone had no effect on CVC relative to the control (all <i>P</i> > 0.104). Both l-NAME and HC030031 + l-NAME reduced CVC (all <i>P</i> < 0.001), with the combined treatment showing a greater reduction (all <i>P</i> < 0.001). We showed that TRPA1 channels mediate cutaneous vasodilation during exercise-heat stress only when NOS is inhibited.<b>NEW & NOTEWORTHY</b> We demonstrated that the administration of TRPA1 channel antagonist HC030031 only appears to attenuate cutaneous vasodilation during exercise in the heat when nitric oxide synthase (NOS) is inhibited. TRPA1 channels may function as a \"backup system\" to maintain cutaneous vasodilation when NOS-dependent vasodilation is compromised during exercise in the heat.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R319-R328"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381549","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":"Metabolic fuel selection in rainbow trout: coping with intralipid infusion.","authors":"Giancarlo G M Talarico, Elie Farhat, Jan A Mennigen, Jean-Michel Weber","doi":"10.1152/ajpregu.00170.2024","DOIUrl":"10.1152/ajpregu.00170.2024","url":null,"abstract":"<p><p>The impact of hyperlipidemia on fuel selection has never been investigated in fish. This study quantifies how intralipid administration affects <i>i</i>) in vivo mobilization of lipids (lipolytic rate: <i>R</i>_a glycerol) and carbohydrates (hepatic glucose production: <i>R</i>_a glucose) in rainbow trout and <i>ii</i>) key proteins involved in the regulation of fuel metabolism that could explain changes in glycerol and glucose kinetics. Results show that intralipid triples lipolytic rate (from 2.5 ± 0.5 to 7.8 ± 1.1 µmol glycerol kg^-1·min^-1) and inhibits glucose production by 36% (from 7.3 ± 0.9 to 4.7 ± 0.4 µmol kg^-1·min^-1). The stimulation of lipolysis is probably driven by lipase activation (gene expression of hormone-sensitive lipase increases in muscle) or by mass action effect. Such a strong lipolytic response is quite surprising because baseline <i>R</i>_a glycerol is already particularly high in fish and is well known for its stability under a variety of stresses that have important effects in mammals. The reduction in trout <i>R</i>_a glucose is likely caused by a large decrease in glycogen mobilization because hepatic gluconeogenic pathway capacity may rise as a consequence of increases in gluconeogenesis gene transcript levels. In contrast to humans, which maintain steady glucose production in response to intralipid infusion, rainbow trout appears to overcompensate increased gluconeogenic capacity with a disproportionately large inhibition of glycogen breakdown. Overall, these intralipid-driven changes in glycerol and glucose kinetics allow fish to decrease their reliance on carbohydrates and amino acids by replacing them, in part, with fatty acids as metabolic fuels.<b>NEW & NOTEWORTHY</b> How do fish respond to an intralipid infusion (a soybean-derived emulsion used for parenteral nutrition of human patients)? In rainbow trout, intralipid administration triples the rate of lipid mobilization (lipolysis) and reduces hepatic glucose production by 36%. These changes in substrate fluxes allow fish to decrease their reliance on amino acids and carbohydrates by substituting them with fatty acids as metabolic fuels.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R306-R318"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063167","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":"Endothelial dysfunction in middle-aged and older men with low testosterone is associated with elevated circulating endothelin-1.","authors":"Matthew C Babcock, Lyndsey E DuBose, Kerry L Hildreth, Brian L Stauffer, Wendy M Kohrt, Megan M Wenner, Kerrie L Moreau","doi":"10.1152/ajpregu.00218.2024","DOIUrl":"10.1152/ajpregu.00218.2024","url":null,"abstract":"<p><p>Low testosterone in middle-aged/older men contributes to accelerated vascular aging, including endothelial dysfunction. However, the mechanisms by which low testosterone affects endothelial dysfunction are not well understood. We sought to determine whether higher endothelin-1 (ET-1) levels are associated with reduced brachial artery flow-mediated dilation (FMD) in middle-aged/older men with low testosterone. Plasma ET-1 was quantified in 60 men categorized as young (<i>n</i> = 20, age = 30 ± 4 yr, testosterone = 510 ± 63 ng/dL), middle-aged/older with normal testosterone (<i>n</i> = 20, age = 59 ± 6 yr, testosterone = 512 ± 115 ng/dL), or middle-aged/older with low testosterone (<i>n</i> = 20, age = 60 ± 8 yr, testosterone = 265 ± 47 ng/dL). Endothelial function was determined via brachial artery FMD. Venous and arterial endothelial cells were harvested via endovascular biopsy in a subset of participants and stained for ET-1 expression. Middle-aged/older men with normal testosterone exhibited lower brachial artery FMD (5.7 ± 2.2%) compared with young men (7.3 ± 1.3%, <i>P</i> = 0.020), which was exaggerated in middle-aged/older men with low testosterone (4.0 ± 1.8%, <i>P</i> = 0.010 vs. middle-aged/older men with normal testosterone). Plasma ET-1 was not different between young (5.6 ± 0.9 ng/dL) and middle-aged/older men with normal testosterone (6.0 ± 1.4 ng/dL, <i>P</i> = 0.681) but was higher in middle-aged/older men with low testosterone (7.7 ± 2.8 ng/dL) compared with both groups (<i>P</i> < 0.001 vs. young men; <i>P</i> = 0.013 vs. middle-aged/older men with normal testosterone). There was no difference in venous (<i>P</i> = 0.616) or arterial (<i>P</i> = 0.222) endothelial cell ET-1 expression between groups. There was a significant inverse association between plasma ET-1 and FMD (<i>r</i> =-0.371, <i>P</i> = 0.004). These data suggest that the accelerated age-associated reduction in endothelial dysfunction in middle-aged/older men with low testosterone is related to higher circulating ET-1.<b>NEW & NOTEWORTHY</b> Middle-aged/older men with low testosterone have reduced vascular endothelial function compared with young and age-matched men with normal testosterone. In this manuscript, we demonstrate that men with low testosterone have higher plasma endothelin-1, which is associated with worse brachial artery flow-mediated dilation. The source of higher plasma endothelin-1 remains unknown; however, higher circulating endothelin-1 appears to be a mechanism contributing to reduced vascular endothelial function in men with low testosterone.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R253-R261"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}