Physiological reports
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Physiological reports · Apr 2017
Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide.
Previously, we reported that 20% fructose diet causes salt-sensitive hypertension. In this study, we hypothesized that a high salt diet supplemented with 20% fructose (in drinking water) stimulates salt-sensitive hypertension by increasing salt retention through decreasing renal nitric oxide. Rats in metabolic cages consumed normal rat chow for 5 days (baseline), then either: (1) normal salt for 2 weeks, (2) 20% fructose in drinking water for 2 weeks, (3) 20% fructose for 1 week, then fructose + high salt (4% NaCl) for 1 week, (4) normal chow for 1 week, then high salt for 1 week, (5) 20% glucose for 1 week, then glucose + high salt for 1 week. ⋯ Sodium excretion was lower in fructose + high salt group compared to high salt only: 5.33 ± 0.21 versus 7.67 ± 0.31 mmol/24 h; P < 0.001). Nitric oxide excretion was 2935 ± 256 μmol/24 h in high salt-fed rats, but reduced by 40% in the 20% fructose + high salt group (2139 ± 178 μmol /24 hrs P < 0.01). Our results suggest that fructose predisposes rats to salt-sensitivity and, combined with a high salt diet, leads to sodium retention, increased blood pressure, and impaired renal nitric oxide availability.
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Physiological reports · Jan 2017
Investigation of the link between fluid shift and airway collapsibility as a mechanism for obstructive sleep apnea in congestive heart failure.
The increased prevalence of obstructive sleep apnea (OSA) in congestive heart failure (CHF) may be associated with rostral fluid shift. We investigated the effect of overnight rostral fluid shift on pharyngeal collapsibility (Pcrit), pharyngeal caliber (APmean), and apnea-hypopnea index (AHI) in CHF patients. Twenty-three optimally treated systolic CHF patients were studied. ⋯ There was no significant change in AHI between the first and second half of the night (first-half: 12.9 ± 12.4/h; second-half: 13.7 ± 13.3/h; P = 0.6). Overnight rostral fluid shift was associated with increased pharyngeal collapsibility and decreased pharyngeal caliber during sleep in CHF patients. Rostral fluid shift may be an important mechanism of OSA in this patient group.
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Physiological reports · Dec 2016
Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice.
Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. ⋯ Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes. In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking.
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Physiological reports · Nov 2016
Haploinsufficiency of the folliculin gene leads to impaired functions of lung fibroblasts in patients with Birt-Hogg-Dubé syndrome.
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder caused by germline mutations in the FLCN gene, and characterized by skin fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax, and renal neoplasms. Pulmonary manifestations frequently develop earlier than other organ involvements, prompting a diagnosis of BHDS However, the mechanism of lung cyst formation and pathogenesis of pneumothorax have not yet been clarified. Fibroblasts were isolated from lung tissues obtained from patients with BHDS (n = 12) and lung cancer (n = 10) as controls. ⋯ Our results suggest that FLCN is associated with chemotaxis in lung fibroblasts. Together with reduced TGF-β1 expression by BHDS lung fibroblasts, a state of FLCN haploinsufficiency may cause lung fibroblast dysfunction, thereby impairing tissue repair. These may reveal one mechanism of lung cyst formation and pneumothorax in BHDS patients.
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Physiological reports · Nov 2016
Inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenine-induced uremic mice with severe hyperparathyroidism.
Patients with chronic kidney disease (CKD) are at increased risk for bone fractures compared with the general population. Repression of the Wnt/β-catenin signaling pathway is associated with bone abnormalities. Inhibition of glycogen synthase kinase (GSK)-3β, a critical component of the Wnt/β-catenin signaling pathway, increases bone volume through accumulation of β-catenin. ⋯ Trabecular bone volume increased in CKD-GSK-3β+/- and CKD+LiCl mice compared with CNT and CKD mice. However, there were no significant differences in cortical bone volume among the three groups of CKD mice. The results suggest that inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenine-induced uremic mice with uncontrolled hyperparathyroidism.