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

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.

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.

Several forebrain and brainstem neurochemical circuitries interact with peripheral, neural, and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Over the past decades, much progress has been made in understanding the complex mechanisms underlying the neuroendocrine control of hydromineral homeostasis. Classical experiments performed by Dr. Antunes-Rodrigues in the early 1960s, such as lesions of hypothalamic and extrahypothalamic areas and drug microinfusions, associated with behavioral analysis and electrolytes/hormones measurements, were crucial to elucidate several aspects of the regulation of hydromineral balance. Fifty years after this pioneering research, the use of immunohistochemistry shifted methodological efforts to the central nervous system, in an attempt to elucidate how neurons (and lately, also glial cells) receive and interpret sensory signals originating from the periphery. This report focuses on the main findings obtained by Dr. Antunes-Rodrigues and colleagues using immunohistochemistry as an important tool in the first two decades of this century to elucidate the brain-specific neurochemical circuits underlying functional mechanisms by which osmotic and volume challenges could impact hormonal and behavioral responses.

Seizures in preterm infants are highly associated with adverse neurodevelopmental outcomes. Clinical diagnosis remains a challenge because seizures in preterm infants are often clinically silent. The present study examined whether seizure-related cardiovascular changes could aid seizure detection. Chronically instrumented preterm fetal sheep at 0.7 gestation received sham hypoxia-ischaemia (HI) (n = 10) or HI induced by 25 min of complete umbilical cord occlusion (n = 10). Fetal electroencephalogram (EEG) recovery and cardiovascular physiology were assessed until 72 h post HI. HI was associated with stereotypic evolving seizure activity starting 14 ± 13 h (mean ± SD) after HI, with an average total seizure count of 42 ± 2, duration 67 ± 25 s, amplitude 187 ± 88 µV, and seizure burden of 150 ± 129 s/h. Individual seizures were associated with increased mean arterial pressure (MAP) (38.2 ± 2.7 to 40.1 ± 3.2 mmHg). The fetal heart rate (FHR) response during seizures was predominantly tachycardia, but either bradycardia or no change was seen in 21% of seizures. Using minute-to-minute variation in MAP and FHR above one standard deviation as thresholds, the presence of seizures on electroencephalogram (EEG) was predicted with a sensitivity of 75.1 ± 30.4% and 66.5 ± 26.2%, respectively. Using MAP and FHR as a composite measure detected 87.1 ± 4.2% of stereotypic seizures. These data suggest that seizure-related transient fluctuations in MAP and FHR are potentially useful biomarkers for electrographic seizure activity.NEW & NOTEWORTHY In preterm fetal sheep, seizures after hypoxia-ischaemia were associated with increased mean arterial pressure and either increased or decreased fetal heart rate. Minute-to-minute variation in mean arterial pressure and fetal heart rate measures detected 75.1 ± 30.4% and 66.5 ± 26.2% of seizures, respectively, whereas together they detected 87.1 ± 4.2%. Assessment of seizure-related cardiovascular changes may help to improve seizure detection in preterm infants.