American journal of physiology. Regulatory, integrative and comparative physiology
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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).
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Jun 2013
Selective inhibition of vagal afferent nerve pathways regulating cough using Nav 1.7 shRNA silencing in guinea pig nodose ganglia.
Adeno-associated virus delivery systems and short hairpin RNA (shRNA) were used to selectively silence the voltage-gated sodium channel NaV 1.7 in the nodose ganglia of guinea pigs. The cough reflex in these animals was subsequently assessed. NaV 1.7 shRNA was delivered to the majority of nodose ganglia neurons [50-60% transfection rate determined by green fluorescent protein (GFP) gene cotransfection] and action potential conduction in the nodose vagal nerve fibers, as evaluated using an extracellular recording technique, was markedly and significantly reduced. ⋯ Stimuli such as capsaicin and bradykinin that are known to stimulate both nodose and jugular C-fibers evoked coughing in conscious animals was unaffected by NaV 1.7 silencing in the nodose ganglia. Nodose C-fiber selective stimuli including adenosine, 2-methyl-5-HT, and ATP all failed to evoke coughing upon aerosol challenge. These results indicate that cough is independently regulated by two vagal afferent nerve subtypes in guinea pigs, with nodose Aδ fibers regulating cough evoked mechanically from the trachea and bradykinin- and capsaicin-evoked cough regulated by C-fibers arising from the jugular ganglia.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2013
Activation of cannabinoid receptor 2 inhibits experimental cystitis.
Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1and CB2). Both CB1 and CB2 are present in bladders of various species, including human, monkey, and rodents, and it appears that CB2 is highly expressed in urothelial cells. We investigated whether treatment with the CB2 agonist GP1a alters severity of experimental cystitis induced by acrolein and referred mechanical hyperalgesia associated with cystitis. ⋯ The inhibitory effects of the CB2 agonist were prevented by the selective CB2 antagonist AM630 (10 mg/kg, sc). We further demonstrated the inhibitory effects of CB2 appear to be at least partly mediated by reducing bladder inflammation-induced activation of ERK1/2 MAPK pathway. The results of the current study indicate that CB2 is a potential therapeutic target for treatment of bladder inflammation and pain in patients.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · May 2013
Prolonged high fat/alcohol exposure increases TRPV4 and its functional responses in pancreatic stellate cells.
The present study investigated transient receptor potential vanilloid type 4 (TRPV4) ion channels in pancreatic stellate cells (PSCs) isolated from rats with high-fat and alcohol diet (HFA)-induced chronic pancreatitis. TRPV4 is a calcium-permeable nonselective ion channel responsive to osmotic changes, alcohol metabolites arachidonic acid, anandamide, their derivatives, and injury-related lipid mediators. Male Lewis rats were fed HFA for 6-8 wk before isolation and primary culture of PSCs. ⋯ Activation responses were attenuated by nonselective TRPV channel blocker ruthenium red. Tumor necrosis factor-α (TNF-α, 1 ng/ml, 16 h) increased responses to 4αPDD in control PSCs. These findings implicate TRPV4-mediated calcium responses inducible after HFA exposure and inflammation in reactive responses of activated PSCs that impair pancreatic function, such as responsiveness to cytokines and the deposition of collagen fibrosis that precipitates ductal blockage and pain.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Mar 2013
A novel murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by immunization with a spermine binding protein (p25) peptide.
The pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is poorly understood. Inflammatory and autoimmune mechanisms may play a role. We developed a murine model of experimental autoimmune prostatitis (EAP) that mimics the human phenotype of CP/CPPS. ⋯ Prostates from p25 99-118-immunized mice demonstrated elevated gene expression levels of TNF-α, IL-17A, IFN-γ, and IL-1β, not observed in control mice. Compared with controls, p25 99-118-immunized mice had significantly higher micturition frequency and decreased urine output per void, and they demonstrated elevated pelvic pain response. p25 99-118 immunization of male SWXJ mice induced prostate-specific autoimmunity characterized by prostate-confined inflammation, increased micturition frequency, and pelvic pain. This autoimmune prostatitis model provides a useful tool for exploring the pathophysiology and new treatments.