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

With rising average global temperatures, extreme heat events are becoming more frequent and intense, placing heat-vulnerable older adults at an elevated risk of mortality and morbidity. We recently showed that a brief 2 h access to air-conditioning during a simulated heatwave confers cytoprotective benefits in older adults; however, air-conditioning is inaccessible to many. Although foot immersion and neck cooling have been proposed as alternative cooling strategies, their effects on cellular stress are unclear. We evaluated cellular responses (autophagy, apoptosis, acute inflammation, and heat shock proteins) in peripheral blood mononuclear cells from 17 participants (9 females, median age: 72 [IQR, 69-74] yr) who completed three, 6-h heat exposures at 38°C (35% relative humidity) with either no-cooling (control), submersion of the feet (mid-calf) in 20°C water for 40-min each hour or foot immersion with a cool wet towel (20°C) around the neck. Core (rectal) temperature was measured continuously. Western blot analysis was used to assess changes in protein responses at baseline and end exposure. Despite similar elevations in core temperature between conditions, p62 concentrations were elevated in the control compared with both foot immersion with [mean difference: 0.4 relative quantity (RQ); P = 0.046] and without (0.6 RQ; P = 0.026) neck cooling. Furthermore, HSP70 concentrations were elevated in control compared with foot immersion (0.7 RQ; P = 0.030). No changes between conditions were observed for apoptotic or inflammatory proteins. Although foot immersion with or without neck cooling had minimal impact on core temperature, these strategies may improve autophagic responses in older adults when exposed to extreme heat.NEW & NOTEWORTHY As the incidence and severity of heatwaves continue to rise, there is an urgent need to develop accessible and sustainable heat-alleviation strategies. We evaluated the use of foot immersion in cool water with or without the addition of a damp towel around the neck on cellular stress responses in older adults exposed to extreme heat. Although neither cooling intervention reduced elevations in core temperature, both cooling strategies may improve autophagic responses in older adults.

We propose the interfacial water quantum-transition (IWQ) model as a novel paradigm explaining temperature-dependent structural and functional transitions (discontinuities) observed in proteins. The central postulate states that experimentally measured critical temperatures, T_C, are related to physical reference temperatures, T_W, defined by rotational quantum transitions of temporarily free water molecules in the protein-water interface. Applicability of this concept is demonstrated with transitions observed in two disparate model systems, viz., hemoglobin and thermosensitive transient receptor potential (TRP) channels. We propose that the same mechanism underlies the definition of basal body temperatures in homeotherms, the reference temperature for humans being T_W = 36.32°C. Specifically, we demonstrate that the body temperatures of both human and chicken (representing the two classes of homeothermic vertebrates) not only coincide with quantum-transition reference temperatures but are also related to pronounced transitions in hemoglobin oxygen saturation. This suggests that the evolution of body temperatures in different homeothermic species might involve an interplay between critical parameters of oxygen supply on the one hand and quantum-physical rotational transition temperatures of water on the other. Casting the IWQ model concept into a concise formula: Proteins sense and water sets critical physiological temperatures.NEW & NOTEWORTHY We propose the interfacial water quantum-transition (IWQ) model to explain how proteins respond to temperature changes through specific quantum transitions of water at the protein-water interface. This model links key functional temperatures, such as human body temperature, to these transitions. By examining proteins like hemoglobin and thermosensitive channels, the IWQ model reveals a fundamental connection between water behavior and biological temperature regulation, shedding light on evolutionary adaptations in humans and animals.

The purpose of this study was to investigate the sex-specific differences in how late-midlife adults respond to short-term disuse and rehabilitation. Sixteen late-midlife adults, who were free of overt disease (8 males: 58 ± 2 yr, BMI 29.4 ± 0.8 kg·m^-2; 8 postmenopausal females: 56 ± 2 yr, BMI 29.1 ± 1.1 kg·m^-2) underwent 7 days of unilateral lower limb suspension (ULLS), followed by 7 days of rehabilitation. Vastus lateralis muscle biopsies were collected before and following ULLS [in both control (CON) and immobilized (IMM) legs] and in the IMM leg post-rehabilitation. We applied deuterium oxide to measure muscle protein synthesis (MPS), immunoblotting to assess mTORC1 signaling, and assessed changes in muscle fiber cross-sectional area (CSA) and leg strength. MPS was 17.8 ± 14.6 and 32.7 ± 10.9% lower in the IMM compared with the CON leg in males (P = 0.32) and females (P < 0.05), respectively, during immobilization. MPS was 27.5 ± 24.5 and 9.7 ± 38.9% higher in the IMM leg during the rehab compared with during the IMM phase in the males and females, respectively (P > 0.05). Leg extension one repetition maximum declined by 24.2 ± 2.4 and 17.1 ± 2.1% in males and females, respectively, after IMM (both P < 0.01), in the IMM leg with no change in the CON leg (P > 0.05). Our data show that late-midlife males and females experience similar reductions in MPS and muscle fiber CSA. Seven days of resistance exercise rehabilitation partially reverses the decline in muscle strength, CSA, and MPS, but longer rehabilitation periods are required for full recovery in late-midlife adults.NEW & NOTEWORTHY This study provides novel data on the average rate of muscle protein synthesis during 7 days of disuse and 7 days of rehabilitation in late-midlife adults. Both sexes experienced a similar reduction in muscle protein synthesis, strength, and fiber cross-sectional area during disuse. Seven days of resistance exercise rehabilitation partially reverses the disuse-induced decline in muscle protein synthesis, strength, and fiber size; however, longer periods of rehabilitation are required for full recovery.

Interactions between the gut microbiota and intestinal barrier may contribute to the pathophysiology of high-altitude illnesses. This study aimed to determine the effects of targeting the gut microbiota using dietary supplementation with a blend of fermentable fibers and polyphenol sources on gut microbiota composition, fecal short-chain fatty acids (SCFAs), and intestinal function and permeability during hypobaric hypoxia exposure. Healthy adults participated in a randomized, placebo-controlled, crossover study. Food products containing oligofructose-enriched inulin, galacto-oligosaccharide, high-amylose corn starch, cocoa, green tea and cranberry extracts, and blueberry powder (FP) or maltodextrin (placebo; PL) were consumed daily during three 2-wk phases separated by a ≥1-wk washout. During the final 36 h of each phase, participants resided in a hypobaric chamber simulating low (LA; 500 m) or high (HA; 4,300 m) altitude creating three experimental conditions: PL + LA, PL + HA, and FP + HA. Twenty-six participants completed ≥1 study phase and 13 [12 male; 21 ± 3 yr; body mass index (BMI) 25.4 ± 2.4 kg/m²] completed all three phases. Results demonstrated that FP mitigated hypoxia-induced increases in intestinal permeability within the small intestine and proximal colon while increasing Bifidobacterium relative abundance and decreasing gut microbiota α-diversity and colonic pH. Higher Bifidobacterium relative abundance and lower colonic pH were associated with greater reductions in intestinal permeability. However, FP did not alter fecal SCFA concentrations and increased gastrointestinal symptoms and altitude sickness during hypobaric hypoxia exposure. Findings suggest that targeting the gut microbiota with a combination of fermentable fibers and polyphenols can prevent hypobaric hypoxia-induced increases in intestinal permeability but that benefit does translate into a reduction in altitude illness symptoms.NEW & NOTEWORTHY Dietary supplementation targeting the gut microbiota may provide novel approaches to improving physiologic responses to environmental stressors such as those experienced during sojourn at high terrestrial altitudes. This study demonstrated that gut microbiota-targeted dietary supplementation using a blend of fermentable fibers and polyphenol sources can prevent hypobaric hypoxia-induced decrements in intestinal permeability. Findings support the emerging concept that the gut microbiota may be a modifiable factor influencing physiologic responses in austere environments.

Aquaporin (Aqp)-10 is an aquaglyceroporin permeable to both water and uncharged small-molecule compounds. In ray-finned fish Aqp10 paralogs, urea and boric acid permeabilities of Aqp10.2-but not its glycerol permeability-are much weaker than those of Aqp10.1 and plesiomorphic Aqp10; however, the molecular mechanisms responsible for urea and boric acid permeabilities remain unclear. In this study, we constructed structural models of these sequences and found that two aromatic amino acid residues at positions 1 and 3 of the four amino acid sites in the aromatic/arginine (ar/R) selectivity filter were important in reducing urea and boric acid permeabilities, but not glycerol permeability. Moreover, the characteristics of these amino acid residues could be quantified by calculating the sum of molecular weights of the two amino acid residues. Site-directed mutagenesis revealed that replacement of one of the two aromatic amino acid residues at positions 1 and 3 in the ar/R region with a small amino acid residue enhanced the urea and boric acid permeabilities of Aqp10. In the examined Aqp10s, sum of the molecular weights of amino acid residues at positions 1 and 3 in the ar/R selectivity filter was inversely correlated with the pore diameter and urea and boric acid permeabilities. Overall, our results indicate that the two bulky amino acid residues in the ar/R selectivity filter contribute to the formation of a filter that influences the urea and boric acid permeabilities of aquaglyceroporins.NEW & NOTEWORTHY Urea and boric acid permeabilities of aquaporin (Aqp)-10.2 are lower than those of Aqp10.1 and plesiomorphic Aqp10, and the molecular weight sum of the two amino acid residues in the aromatic/arginine (ar/R) selectivity filter plays a filtering role that affects permeability. Therefore, urea and boric acid permeabilities of Aqp10s can be assessed using the sum of the molecular weights of the two amino acids in the ar/R region, which represents a significant advancement in this field.

Habituation, a pattern of cold acclimatization, is characterized by a reduction in peripheral vasoconstriction and a subsequent increase in skin temperature (T_sk) during cold exposure. Habituation is achieved through repeated reductions in T_sk and is likely mediated by attenuated sympathetic activation. However, the effectiveness of habituation in alleviating the deleterious effects of cold on peripheral temperatures, thermal comfort, and hand function is unclear. Furthermore, the mechanisms by which habituation may improve extremity (hand and forearm) responses to cold are unclear. Ten healthy humans (8 male/1 female/1 female to male) underwent 8 days of repeated cold air exposure (8°C, 2 h/day). At baseline (1-2 wk prior) and on days 1 and 8, mean and extremity T_sk and skin blood flow (SkBF; laser-Doppler flowmetry) were recorded continuously. Thermal comfort was recorded at regular intervals, and manual dexterity was measured before and at the end of each exposure. At baseline, the day before, and the day following repeated exposure, reflex cutaneous vasoconstriction was elicited using a water-perfused suit (mean T_sk ∼33.5 to 30.5°C), whereas SkBF was recorded at a thermoneutral (uncovered) forearm skin site. In cold air, T_sk and SkBF decreased over time on each day (P < 0.05) but did not differ across days (P > 0.05). Thermal comfort and dexterity decreased in the cold (P < 0.05) but were largely unaltered across days (P > 0.05). Reflex vasoconstriction was unaffected by repeated exposure (baseline: 69.3 ± 26.0, pre: 65.2 ± 32.4, and post: 50.8 ± 31.0%CVC·°C AUC; P = 0.07). We therefore conclude that eight consecutive days of cold air exposure do not augment T_sk, thermal comfort, or manual dexterity in the cold.NEW & NOTEWORTHY In this study, we showed that 8 days of consecutive cold air exposure does not alter skin temperature, reflex vasoconstrictor responsiveness, thermal perception, or hand dexterity. These novel findings indicate that short-term repeated cold air exposure is unlikely to result in physiological adaptations that effectively increase extremity perfusion, temperature, or function.

Hypertension is more prevalent in males than age-matched premenopausal females. Average sodium intake in the United States is higher than recommended and is a risk factor for developing hypertension. Sex differences in renal sodium homeostasis may underlie sex differences in hypertension prevalence. For example, renal endothelin-1 (ET-1) plays a key role in the maintenance of blood pressure and sodium homeostasis. Previous rodent studies demonstrate that females excrete higher urinary ET-1 compared with males, and increasing dietary sodium promotes urinary ET-1 excretion only in male rats. However, the impact of sex on sodium and renal ET-1 signaling in humans is unclear. Therefore, we aimed to determine whether the renal ET-1 system responds differently to salt loading in male and female human research participants. To test our hypothesis, normotensive salt-resistant male and female participants were administered a low (1 g/day), recommended (2.3 g/day), and high (7 g/day) sodium diet for 10 days each in random order. The 24-h urine samples were collected and assessed for sodium and ET-1. Following increased dietary sodium, both males and females increased urinary sodium excretion (diet: P < 0.001). Following increased dietary sodium, participants exhibited an increased urinary ET-1 excretion (diet: P = 0.038). Interestingly, post hoc testing revealed that only females displayed an increase in ET-1 excretion (recommended vs. high sodium, P = 0.009). Overall, the current human study provides novel insights into potential sex-specific modulation of ET-1 and renal responses to dietary sodium. Further investigations are warranted to understand the underlying molecular mechanisms driving sex-related differences in renal ET-1 signaling and sodium handling.NEW & NOTEWORTHY To our knowledge, this is the first human study detailing sex differences in the renal endothelin-1 (ET-1) system in response to increasing sodium diets. We found that increasing dietary sodium intake increases urinary ET-1 excretion, an effect that appeared to be specific to females, not males. These data highlight important sex differences in a key natriuretic mechanism, potentially modulating sex differences in the prevalence of hypertension. Further studies are needed to confirm our findings and provide mechanistic insight.

Postoperative ileus (POI) is a prevalent complication resulting from an imbalance in sympathetic activity or dysregulation of the intestinal immune system. Research has shown that interactions between the peripheral nervous system and immune system modulate intestinal functions. Electroacupuncture (EA) has been shown to ameliorate gastrointestinal dysmotility in patients with POI; however, the specific pathways and molecular mechanisms underlying its effects remain unclear. Here, we reported the signaling pathways that mediate the regulatory effects of EA in POI. Our findings indicated that EA ameliorated gastrointestinal dysmotility, inhibited celiac sympathetic overactivation, and reduced norepinephrine (NE) release. Notably, NE released by the sympathetic nerve terminals regulates the immune system primarily via its stimulation of α2-adrenoceptors (α2-ARs). α2-ARs could regulate macrophage activation in POI and were the key receptors for macrophages to perform neuroimmunomodulatory functions. Furthermore, sympathectomy and α2-ARs antagonist could mimic the improvement effects of EA on gastrointestinal motility and inflammatory response. Our findings demonstrated the pivotal function of the NE-α2-ARs signaling pathways in the modulation of POI, potentially contributing to the development of EA-based therapeutic interventions for gastrointestinal dysmotility disorders after surgery.NEW & NOTEWORTHY Electroacupuncture (EA) ameliorated gastrointestinal dysmotility and inhibited celiac sympathetic overactivation. The α2-adrenergic signaling pathway was involved in the regulation of gastrointestinal dysmotility and was regulated by EA stimulation. The α2-adrenoceptors (α2-ARs) regulated the activation of macrophages in postoperative ileus (POI). The improvement of EA in gastrointestinal motility was mimicked by sympathectomy and α2-adrenoceptors antagonist.

Individuals with masked hypertension have out-of-office blood pressure (BP) readings in the hypertensive range, but office BP readings below the hypertensive cutoff, making masked hypertension less likely to be diagnosed. The aim of this study was to determine whether in-laboratory measurements of BP and vascular function in response to exercise can serve as indicators of masked hypertension in young adults. Thirty-three young men with office BP <130/80 mmHg, free of smoking and clinical diseases, were included in this study. All participants underwent 24-h ambulatory BP monitoring for BP classification, as well as in-laboratory BP and vascular assessments at rest and after a maximal graded exercise test on a cycle ergometer. These assessments included peripheral and central BP, arterial stiffness, wave reflection, and endothelial function. Compared to participants without masked hypertension (CON; n = 17), those with masked hypertension (MH; n = 16) had a higher level of 24-h, daytime, and nighttime systolic BP (P ≤ 0.005), but similar office BP (P ≥ 0.5). No differences between groups were found in peripheral BP and vascular function measurements at baseline (P ≥ 0.2) and in response to exercise (P ≥ 0.2 for group by time interaction effects). Although central systolic BP at rest was similar between groups (P = 0.17), MH had a higher marginal mean of central systolic BP from resting, following exercise, and during recovery (MH vs. CON: 113 ± 2 vs. 108 ± 2 mmHg, P = 0.047 for group effect). These findings suggest that in young men, masked hypertension may be associated with an elevated central systolic BP, which could be induced by exercise.NEW & NOTEWORTHY We show for the first time that in young men, peripheral blood pressure (BP) and vascular function in response to maximal graded exercise tests were not different between individuals with and without masked hypertension. On the other hand, in young men, masked hypertension may be associated with an elevated central systolic BP, which could be induced by exercise.