Current research in physiology最新文献

The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the vascular resistance. In the first protocol the sequence of antagonists was methyl-atropine followed by propranolol and then by prazosin, while in the second protocol the sequence was propranolol followed by methyl-atropine and then by prazosin. In SH the baseline heart rate was significantly lower than in control mice and the antagonism of the parasympathetic and sympathetic tone to the heart in both experimental protocols indicated an increased parasympathetic tone in SH mice and no changes in the sympathetic tone. Antagonism of the sympathetic tone to the vascular resistance with prazosin produced similar changes in arterial pressure in control and SH mice. Altogether these findings support the concept that mice submitted to SH present a significant increase in the parasympathetic but not in the sympathetic tone, which may explain why the baseline arterial pressure was not increased in SH mice.

Background

To investigate how rapid changes in hydration affect urine color expressed in CIE L*a*b* colorspace.

Methods

This study was a two-day crossover design where subjects (N = 30) came in one visit dehydrated, after a 15 h overnight fluid deprivation, and rapidly rehydrated by drinking at least 1000 mL of water in 2 h. On the other visit subjects reported euhydrated and then rapidly dehydrated 2% by walking (3 mph) in a heat chamber (100°F, 50% humidity) for 2 h. Urine samples on both days were collected pre- and post-dehydration/rehydration. Urine osmolality, urine specific gravity, subjective urine color and objective urine color expressed in CIE L*a*b* colorspace were measured.

Results

In the dehydration trial participants experienced a significant weight loss of approximately 2% of their starting, euhydrated body weight. The CIE urine color L*-value significantly decreased (−2.3 units) while the b*-value significantly increased (16 units). Subjective urine color significantly increased (1 unit). Urine osmolality increased (25 mmol/kg) and urine specific gravity increased (0.002 g/mL) between the pre- and post-dehydration conditions, however, neither of these changes were statistically significant. In the rehydration trial participants had a significant 1.5% increase in body weight after the ingestion of water. Significant increases were observed in the CIE urine color L*-value (7 units) and a*-value (1.1 units), while the b*-value significantly decreased (−24 units). Subjective urine color significantly decreased (−3 units). Urine osmolality (−600 mmol/kg) and urine specific gravity (−0.018 g/mL) significantly decreased between the pre- and post-rehydration conditions.

Conclusions

Traditional markers of hydration, including urine osmolality and urine specific gravity, did not significantly change in the acute dehydration trial, suggesting that these values may not be responsive to rapid changes in hydration status. However, the CIE L*- and b*-values of urine color significantly decreased in the rapid dehydration trial and significantly increased in the rapid rehydration trial. Thus, the results of the current study suggest that urine color L*- and b*-values expressed in the CIE L*a*b* colorspace were more responsive to changes in hydration status during rapid dehydration than traditional indices of urine concentration and thus may be better markers under such conditions.

Background

The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) in vitro. We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca²⁺ release and whether this effect is linked to a change in RyR2 phosphorylation.

Methods

& Results: Human embryonic kidney (HEK293) cells with inducible RyR2 expression were treated with the cGMP analogue 8-Br-cGMP (100 μM) to activate endogenous PKG. In cells transfected with luminal Ca²⁺ sensor, D1ER, PKG activation significantly reduced the threshold for RyR2-mediated spontaneous Ca²⁺ release (93.9 ± 0.4% of store size with vehicle vs. 91.7 ± 0.8% with 8-Br-cGMP, P = 0.04). Mutation of the proposed PKG phosphorylation sites, S2808 and S2030, either individually or as a combination, prevented the decrease in Ca²⁺ release threshold induced by endogenous PKG activation. Interestingly, despite a functional dependence on expression of RyR2 phosphorylation sites, 8-Br-cGMP activation of PKG did not promote a detectable change in S2808 phosphorylation (P = 0.9). Paradoxically, pharmacological inhibition of PKG with KT 5823 (1 μM) also reduced the threshold for spontaneous Ca²⁺ release through RyR2 without affecting S2808 phosphorylation. Silencing RNA knockdown of endogenous PKG expression also had no quantifiable effect on RyR2 S2808 phosphorylation (P = 0.9). However, unlike PKG inhibition with KT 5823, PKG knockdown did not alter spontaneous Ca²⁺ release propensity or luminal Ca²⁺ handling.

Conclusion

In an intact cell model, activation of endogenous PKG reduces the threshold for RyR2-mediated spontaneous Ca²⁺ release in a manner dependent on the RyR2 phosphorylation sites S2808 and S2030. This study clarifies the regulation of RyR2 Ca²⁺ release by endogenous PKG and functionally implicates the role of RyR2 phosphorylation.

The aim of this study was to determine the effect of voluntary wheel running (VWR) during weight-loss on hepatic lipid and inflammatory biomarkers using a murine model. To induce obesity, male C57Bl/6 mice were fed a 60% high-fat diet (HF) for 10 weeks. At 10 weeks, weight-loss was promoted by randomizing HF-fed mice to a normal diet (ND) either with (WL + VWR) or without (WL) access to running wheels for 8 weeks. Age-matched dietary control mice were fed either a ND or HF for 18 weeks. Following weight-loss, WL + VWR had a lower body mass compared to all groups despite an average weekly caloric consumption comparable to HF mice. WL + VWR had an increased adiponectin concentration when compared to WL, but no difference between WL and WL + VWR was observed for plasma glucose and lipid biomarkers. When compared to HF, the lower hepatic total lipids in both WL and WL + VWR were associated with increased pAMPK:AMPK and reduced pACC-1:ACC-1 ratios. When compared to WL, WL + VWR resulted in lower hepatic cholesterol and trended to lower hepatic triglyceride. In both WL and WL + VWR, pNF-κB p65:NF-κB p65 ratio was lower than HF and comparable to ND. TGFβ1 and BAMBI protein levels were evaluated as biomarkers for hepatic fibrosis. No differences in TGFβ1 was observed between groups; however, WL and WL + VWR had BAMBI protein levels comparable to ND. Overall, the addition of voluntary exercise resulted in greater weight-loss and improvements in hepatic cholesterol and triglyceride levels; however, limited improvements in hepatic inflammation were observed when compared to weight-loss by diet alone.

The interest in nutritional strategies that may counteract the deleterious oxidative effects induced by strenuous exercises is remarkable. Herein, the impact of white tea (Camellia sinensis) (WT), a polyphenol-rich beverage, on antioxidant status in endurance-trained rats after one session of exhaustive exercise were evaluated. Male Wistar rats were divided into groups, which received: control groups - water, and testing groups - WT1 (0.25%; w/v) or WT2 (0.5%; w/v). Drinks were consumed, ad libitum, for 5 or 10 weeks, concomitantly with the running training. Exhaustive running tests were applied before and after the experimental periods. WT intake increased the serum antioxidant capacity of rats in a dose-dependent manner (P < 0.001), which was unaccompanied by the activity of endogenous antioxidant enzymes SOD, GPx, and GR, and GSH content. Inflammatory markers in serum [IL-1β (P = 0.004) and IL-6 (P = 0.001)] could be downregulated by tea intake. In liver tissue, lower levels of lipid oxidation (P < 0.05) and improved antioxidant defenses (SOD, GPx, GR, and GSH, P < 0.05) were related to the consumption of WT in both doses, supporting protective effects in this responsible metabolic organ. In conclusion, long-term consumption of WT could be a promising adjuvant to exercise-stress management, emphasizing its ability to regulate antioxidant responses and prevent oxidative tissue damage.

No studies have examined the effects of cold temperatures (∼0–1 °C) on in vivo cardiac function and control, and metabolism, in salmonids. Thus, we examined: 1) how acclimation to 8 °C vs. acclimation (>3 weeks) or acute exposure (8-1 °C at 1 °C h⁻¹) to 1 °C influenced cardiorespiratory parameters in resting Atlantic salmon; and 2) if/how the control of cardiac function was affected. Oxygen consumption ($\dot{M}{O}_2$) and cardiac function [i.e., heart rate (f_H) and cardiac output ($\dot{Q})$] were 50% lower in the acutely cooled and 1^oC-acclimated salmon as compared to 8 °C fish, whereas stroke volume (V_S) was unchanged. Intrinsic f_H was not affected by whether the fish were acutely exposed or acclimated to 1 °C (values ∼51, 24 and 21 beats min⁻¹ in 8 and 1 °C-acclimated fish, and 8-1 °C fish, respectively), and in all groups f_H was primarily under adrenergic control/tone (cholinergic tone 13–18%; adrenergic tone 37–70%). However, β-adrenergic blockade resulted in a 50% increase in V_S in the 1^oC-acclimated group, and this was surprising as circulating catecholamine levels were ∼1–3 nM in all groups. Overall, the data suggest that this species has a limited capacity to acclimate to temperatures approaching 0 °C. However, we cannot exclude the possibility that cardiac and metabolic responses are evoked when salmon are cooled to ∼ 0–1 °C, and that this prevented further declines in these parameters (i.e., they ‘reset’ quickly). Our data also provide further evidence that V_S is temperature insensitive, and strongly suggest that changes in adrenoreceptor mediated control of venous pressure/capacitance occur when salmon are acclimated to 1 °C.

Blebbistatin potently inhibits actin-myosin interaction, preventing contractile activity of excitable cells including cardiac myocytes, despite electrical excitation of an action potential (AP). We collected intracellular microelectrode recordings of pacemaker cells located in the sinoatrial region (SAR) of the zebrafish heart at room temperature and during acute warming to investigate whether or not blebbistatin inhibition of contraction significantly alters pacemaker cell electrophysiology. Changes were evaluated based on 16 variables that characterized the AP waveform. None of these AP variables nor the spontaneous heart rate were significantly modified with the application of 10 μM blebbistatin when recordings were made at room temperature. Compared with the control group, the blebbistatin-treated group showed minor changes in the rate of spontaneous diastolic depolarization (P = 0.027) and the 50% and 80% repolarization (P = 0.008 and 0.010, respectively) in the 26°C–29°C temperature bin, but not at higher temperatures. These findings suggest that blebbistatin is an effective excitation-contraction uncoupler that does not appreciably affect APs generated in pacemaking cells of the SAR and can, therefore, be used in zebrafish cardiac studies.

Owing to the unfamiliar environment, recreational and professional diving is confronted with several challenges. Usage of self-contained under-water breathing apparatuses during the dive provides the indispensable breathing gas supply for the diver. Instead of air, oxygen-enriched breathing gases (EANx or nitrox) are used with increasing frequency. Unfortunately, their usage implies negative effects because the elevated oxygen partial pressure (pO₂) increases oxidative stress. As a result, the increased formation of reactive oxygen species exerts negative effects on the central nervous system, lungs, vasculature and eyes. However, these disadvantages can be avoided if appropriate rules are followed, e.g. a pO₂<1.4 bar. EANx breathing gases have, on the other hand, major advantages as they help reducing narcotic nitrogen effects and bubble formation.

Several land-based studies had proven a reduced ventilation of exercising subjects if EANx was used instead of air. As breathing gas is the most valuable under-water good, we wanted to translate the on-land results into under-water results. Appropriate studies now demonstrate a novel EANx property as under-water ventilation is also reduced with EANx. In this short communication, we present this additional advantage of EANx-breathing. This benefit seems to be of particular importance as it delays unforeseen running-out-of-gas and thus, contributes to further improving diving safety.

The mechanisms involved in urinary bladder control are not fully understood, but it is well accepted that a complex central network is involved in micturition control. The micturition reflex can be modulated by direct cortical influence through facilitatory and inhibitory mechanisms. In addition, humoral mechanisms are involved in the bladder control. Vasopressin increases bladder contraction and intravesical pressure. This study sought to investigate the effect of intravenous injections of vasopressin receptor antagonists on cystometric parameters in anesthetized female rats. Isoflurane anesthetized adult female Wistar rats underwent femoral artery and vein cannulation for arterial pressure (AP) and heart rate (HR) recordings, and infusion of drugs, respectively. The bladder was also cannulated for intravesical pressure (IP) recordings and infusion of saline (10 mL/h) for cystometric evaluation. After baseline AP, HR and IP recordings, saline (vehicle, 1 mL/kg), V1a (5 μg/kg) or V2 receptor antagonist (5 μg/kg) was injected i.v. and after 25 min the cystometry was carried out. Neither saline nor V1a or V2 receptor blockade evoked any change in AP, HR and IP. Nevertheless, during cystometry, the threshold pressure of the micturition reflex was significantly reduced in rats with V1a (to 19.30 ± 2.39 mmHg) and V2 receptor blockade (to 19.88 ± 2.49 mmHg) compared to the saline group (28.85 ± 2.06 mmHg, p = 0.014). No difference was observed in the other cystometric parameters. Therefore, the data suggest that blockade of V1a and V2 receptors reduces the threshold pressure of the micturition reflex and does not influence other cystometric parameters in anesthetized female Wistar rats.

The heart is endowed with reflexogenic areas capable of powerful blood pressure responses. Relatively little work has studied the hemodynamic mechanisms underlying these responses and whether these are sexually dimorphic. We hypothesized that activation of bradykinin-sensitive pericardial afferents would produce a sexually dimorphic cardiac output response. Male and female Sprague Dawley rats were anesthetized and instrumented with catheters for recording arterial pressure, with an aortic arch flow probe to record cardiac output and with a catheter in the pericardial sac. Mean arterial pressure (MAP), cardiac index (CI) and total peripheral resistance index (TPRI) responses to pericardial bradykinin injection (0.1, 1 μg/kg) were recorded. Pericardial bradykinin injection caused similar increases in MAP in male and female rats. However, the underlying hemodynamic patterns varied considerably. We identified a cluster of CI responders and TPRI responders in both male and female rats. Within CI responders, females exhibited greater CI increases than males. Conversely, in TPRI responders, males exhibited a greater TPRI increase than females. We conclude that aggregate activation of bradykinin-sensitive pericardial afferents is associated with a relatively uniform pressor response but different hemodynamic patterns with males exhibiting a more robust vascular response and females a more robust cardiac output response.