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

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.

Understanding how a sleeve gastrectomy (SG) achieves metabolic improvement is challenging due to the complex relationship between the liver, bile acid (BA) pool, and gut microbiome. We hypothesized that SG alters the gut microbiome, which then increases the BA pool, leading to metabolic efficacy. We performed fecal material transfer (FMT) from SG or sham mice to surgically naïve mice with an intact microbiome. We evaluated the effect of surgery and FMT on BA-related liver enzymes, BA concentrations, and gut microbiome composition via 16S and metagenomic analysis. SG significantly deflected weight gain compared with sham surgery, 5 ± 2 g versus 10 ± 3 g, respectively (P = 0.004). SG significantly increased the BA pool and decreased liver transcription of slc10a1 (P = 0.04) and cyp8b1 (P = 0.03). Random forest analysis identified several features with significantly increased relative abundance in SG compared with sham mice, including Lactobacillus. Examination of metabolic profiles with metagenomic analysis revealed a BA salt hydrolase produced by the Ligilactobacillus species. FMT of SG stool to surgically naïve mice significantly decreased the BA pool compared with sham FMT (P = 0.034). Unlike SG surgery, we found no effect of SG or sham FMT on bile acid-related enzymes in the liver after 14 wk of treatment. Overall, we propose that the metabolic benefits of SG surgery are related to decreased liver transcription of cyp8b1 and slc10a1 with subsequent increases in the systemic and enterohepatic BA pool, including lithocholic acid. The gut microbiome adapts to the altered BA pool with associated increases in Ligilactobacillus and bile salt hydrolase production.NEW & NOTEWORTHY We propose that the metabolic benefits of sleeve gastrectomy are initiated by decreased liver transcription of cyp8b1 and slc10a1. A notable downstream effect includes changes in systemic bile acid composition and circulation, including increased LCA. An altered gut microbiome after surgery includes increases in Ligilactobacillus that was shown to express a bile salt hydrolase, which could be a contributor to the post-sleeve gastrectomy gut microbiome changes.

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.

During systemic acid-base disturbances, the respiratory system modulates CO₂ elimination, whereas the urinary system modulates H⁺ secretion-responses that tend to stabilize arterial pH (pH_a). Proximal tubules (PTs) are responsible for ∼80% of renal H⁺ secretion. Isolated PTs appear to sense and respond to acute changes in basolateral [CO₂] or [[Formula: see text]] using a mechanism that signals through apical angiotensin II AT_1A receptors. In the present study, we examine the whole animal responses to both respiratory acidosis (RAc: ↑[CO₂] → ↓pH_a) and metabolic acidosis (MAc: ↓[[Formula: see text]] → ↓pH_a) in wild-type (WT) versus AT_1A knockout (KO) mice. After catheterizing the carotid artery, we serially sample blood for arterial blood-gas analyses. We find that, in mice breathing 8% CO₂, pH_a reaches a nadir at ∼5 min, and begins to recover after ∼4 h, reaching its maximal value by ∼24 h. Surprisingly, we find that the KO of AT_1A does not affect RAc compensation. During MAc (1% NH₄Cl in drinking water), WT males exhibit only a small/insignificant fall in pH_a, whereas WT females exhibit a larger/significant pH_a decrease. In another sexual dimorphism, AT_1A-KO males acidify on day 2 of MAc, but nearly recover by day 7, whereas KO females exhibit either of two responses: 1) adaptive, in which pH_a falls relatively little by day 2 and then recovers by day 7, and 2) maladaptive, in which pH_a falls at day 2 and remains depressed at day 7. Thus, AT_1A is crucial for defense against MAc in all but half the females, but not RAc.NEW & NOTEWORTHY Here, for the first time, we report that the compensatory response to respiratory acidosis (RAc) in conscious mice concludes within 24 h. Interestingly, during the assessment of metabolic acidosis (MAc), we show that WT males are more adaptive than females, and observe two subpopulations of AT_1A-KO females. From measurements of arterial pH, we conclude that AT_1A is not necessary for the compensation to RAc, but is necessary in the response to MAc.

This study aimed to investigate the efficacy of different electrical waveforms in suppressing bladder overactivity during acute tibial nerve stimulation (TNS) in cats. Cystometric measurements were performed during intravesical infusion of either acetic acid (AA) or normal saline (NS) control solution. Bipolar hook electrodes were implanted on the left tibial nerve for stimulation. TNS with monophasic square waves, biphasic square waves, sine waves, and triangular waves were applied consecutively. Cystometrograms were utilized to evaluate the impacts of these different waveforms on the micturition reflex. Under physiological conditions, all four TNS waveforms significantly increased bladder capacity compared with NS control levels (10.96 ± 3.33 mL; P < 0.001). The relative increases were as follows: 151.10% ± 4.66%, 132.20% ± 3.47%, 131.30% ± 4.85%, and 128.60% ± 3.55% of control values. Under pathological conditions, the monophasic square wave demonstrated inhibitory effects compared with the other three waveforms (P < 0.001). In contrast, no significant differences in inhibitory efficacy were observed between waveforms under pathological conditions (P > 0.05). Quantitative analysis revealed significantly lower T values for both monophasic and biphasic square waves compared with sinusoidal and triangular waveforms (P < 0.001). Furthermore, the triangular wave exhibited significantly higher T values than the sine wave (P = 0.02). The efficacy of TNS waveforms showed condition-dependent variation, with no consistent performance pattern between physiological and pathological states. When considering practical clinical application factors, including stimulator longevity and minimization of tissue damage, the biphasic square wave may be more beneficial.NEW & NOTEWORTHY In this study, we determined the effects of tibial nerve stimulation (TNS) at different stimulation waveforms on bladder reflex in cats. Innovations are as follows: 1) as far as we know, the effects of TNS with different waveforms on overactive bladder has been not explored forever. 2) Our results may provide a basis for altering parameters to improve the therapeutic efficacy of TNS for overactive bladder.

Preeclampsia is a serious pregnancy complication and increases the risk of cardiovascular disease in offspring later in life. Cardiac development includes maturation of cardiomyocytes, a process that is intricately dependent on proper mitochondrial function. However, it remains unclear whether preeclampsia impairs mitochondrial function and alters cardiac maturation of fetal hearts during late gestation. Herein we induced selective reduced uterine placental perfusion (sRUPP), as a model of preeclampsia in rats, to investigate fetal cardiac myosin heavy chain (MYH) expression, reactive oxygen species (ROS) production, mitochondrial respiration, mitochondrial content, and dynamics in male and female fetuses at gestational day 20 (GD 20) (term = GD 22). Litter size was reduced, whereas pup reabsorptions were increased in sRUPP compared with sham controls. In only the male fetuses of sRUPP dams, cardiac Myh7/Myh6 ratio was reduced and Myh6 expression increased. Complex IV activity was elevated in sRUPP male fetuses, with no changes in mitochondrial citrate synthase or ATP synthase activities in either sex. However, ROS production increased in only sRUPP female fetuses. In male fetal hearts, sRUPP increased fusion protein MFN1 expression, tended to decrease fusion protein OPA1 expression, and decreased fission protein FIS1 expression. In contrast, MFN2 and OPA1 were reduced in sRUPP female fetuses. In conclusion, the sRUPP model of preeclampsia affected cardiac maturation and mitochondrial function in late gestation fetuses in a sex-specific manner. As prenatal strategies are being developed to improve pregnancy outcomes, sex-specific fetal effects should be taken into consideration.NEW & NOTEWORTHY This study assessed the impact of preeclampsia on late gestation fetal cardiac development using a rat model of reduced uterine placental perfusion. Our findings revealed sex-specific differences: male fetuses exhibited accelerated cardiac maturation and complex IV activity, whereas female fetuses showed evidence of oxidative stress in the cardiac tissue. Disruptions in mitochondrial dynamics were observed in both sexes. These results underscore the necessity of considering sex-specific fetal effects when developing prenatal therapeutic interventions for preeclampsia.

The cerebral vascular resistance index (CVRi), a single-parameter model based on systemic blood pressure rather than cerebral perfusion pressure (CPP), is widely used to assess cerebrovascular resistance. However, it does not accurately reflect the pressure-flow/velocity relationships in the cerebral circulation, as cerebral blood flow (CBF) is primarily regulated by CPP. This study evaluated the validity of CVRi during orthostatic stress induced by head-up tilt (HUT), which alters CPP independently of arterial blood pressure at the heart level and CBF. Twenty young, healthy participants (aged 23 ± 3 yr) were included, and vascular tone indices, CVRi, critical closing pressure (CrCP), resistance-area product (RAP), and pulsatility index (PI) were measured during HUT. HUT significantly increased CVRi and CrCP (P ≤ 0.003) but did not affect RAP and PI (P ≥ 0.277). However, correlation analysis between changes in CVRi and other vascular indices (i.e., CrCP, RAP, and PI), calculated as the difference between HUT and supine positions, revealed no significant relationships (all r = 0.189-0.701; all P = 0.090-0.425). Moreover, the CVRi response to orthostatic stress differed from that of the corrected CVRi during HUT, which accounts for changes in hydrostatic pressure. Specifically, CVRi increased during HUT (P = 0.003), whereas corrected CVRi, adjusted for changes in hydrostatic pressure, significantly decreased (P < 0.001). These findings highlight the limitations of CVRi, which fails to account for deviations in CPP from systemic blood pressure or for other physiological factors (e.g., intracranial pressure), potentially leading to inaccuracies in estimating cerebral vascular resistance.NEW & NOTEWORTHY CVRi is a useful index for estimating cerebral vascular resistance, as it can be easily calculated using middle cerebral artery blood velocity and systemic blood pressure. However, the results of the present study suggest that, due to physiological variations, particularly conditions in which cerebral perfusion pressure deviates from systemic blood pressure (e.g., during orthostatic stress), CVRi may not accurately reflect true cerebral perfusion pressure. Researchers should be mindful of this limitation.