American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Sep 2013
Comparative StudyThiosulfate: a readily accessible source of hydrogen sulfide in oxygen sensing.
H2S derived from organic thiol metabolism has been proposed serve as an oxygen sensor in a variety of systems because of its susceptibility to oxidation and its ability to mimic hypoxic responses in numerous oxygen-sensing tissues. Thiosulfate, an intermediate in oxidative H2S metabolism can alternatively be reduced and regenerate H2S. We propose that this contributes to the H2S-mediated oxygen-sensing mechanism. ⋯ H2S production was only observed when tissues were hypoxic; exposure to room air, or injecting oxygen inhibited H2S production and resulted in net H2S consumption. Both DTT and DHLA augmented HPV, and DHLA dose-dependently relaxed precontracted mouse and rat aortas. These results indicate that thiosulfate can contribute to H2S signaling under hypoxic conditions and that this is not only a ready source of H2S production but also serves as a means of recycling sulfur and thereby conserving biologically relevant thiols.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Sep 2013
ReviewVentilator-induced diaphragm dysfunction: cause and effect.
Mechanical ventilation (MV) is used clinically to maintain gas exchange in patients that require assistance in maintaining adequate alveolar ventilation. Common indications for MV include respiratory failure, heart failure, drug overdose, and surgery. Although MV can be a life-saving intervention for patients suffering from respiratory failure, prolonged MV can promote diaphragmatic atrophy and contractile dysfunction, which is referred to as ventilator-induced diaphragm dysfunction (VIDD). ⋯ Recent investigations have identified calpain, caspase-3, autophagy, and the ubiquitin-proteasome system as key proteases that participate in MV-induced diaphragmatic proteolysis. The challenge for the future is to define the MV-induced signaling pathways that promote the loss of diaphragm protein and depress diaphragm contractility. Indeed, forthcoming studies that delineate the signaling mechanisms responsible for VIDD will provide the knowledge necessary for the development of a pharmacological approach that can prevent VIDD and reduce the incidence of weaning problems.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Aug 2013
Estradiol modulates recovery of REM sleep in a time-of-day-dependent manner.
Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. ⋯ By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Jul 2013
Adenosine A(2A) receptors regulate the activity of sleep regulatory GABAergic neurons in the preoptic hypothalamus.
The median preoptic nucleus (MnPN) and the ventrolateral preoptic area (VLPO) are two hypothalamic regions that have been implicated in sleep regulation, and both nuclei contain sleep-active GABAergic neurons. Adenosine is an endogenous sleep regulatory substance, which promotes sleep via A1 and A2A receptors (A2AR). Infusion of A2AR agonist into the lateral ventricle or into the subarachnoid space underlying the rostral basal forebrain (SS-rBF), has been previously shown to increase sleep. ⋯ The induction of Fos-IR in preoptic GABAergic neurons was not secondary to drug-induced sleep, since CGS-21680 delivered to the SS-rBF significantly increased Fos-IR in MnPN and VLPO neurons in animals that were not permitted to sleep. Intracerebroventricular infusion of ZM-241385, an A2AR antagonist, during the last 2 h of a 3-h period of sleep deprivation caused suppression of subsequent recovery sleep and reduced Fos-IR in MnPN and VLPO GABAergic neurons. Our findings support a hypothesis that A2AR-mediated activation of MnPN and VLPO GABAergic neurons contributes to adenosinergic regulation of sleep.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Jun 2013
Comparative StudyRole of pituitary in K+ homeostasis: impaired renal responses to altered K+ intake in hypophysectomized rats.
The kidneys maintain extracellular K⁺ homeostasis by altering K⁺ excretion to match K⁺ intake. Because this can occur without changes in plasma K⁺ concentrations ([K⁺]), how the kidneys sense K⁺ intake is unclear. We tested the hypothesis that the pituitary plays a critical role in signaling K⁺ intake to the kidneys. ⋯ In Hypox rats, whereas absorptive renal K⁺ excretion was changed in response to changes in K⁺ intake, postabsorptive K⁺ excretion was not responsive (P < 0.001), indicating impaired renal responses to altered K⁺ intake. In addition, Hypox rats, compared with control rats, showed K⁺ intolerance (increases in plasma [K⁺]) upon feeding (i.e., K⁺ intake) at night or following an intravenous K⁺ infusion (P < 0.01), indicating an impairment of acute renal responses to K⁺ intake. These data support that the pituitary plays a key role in the signaling of K⁺ intake to the kidneys (and kidney responses to altered K⁺ intake).