Hyponatremia-Induced Osteoporosis

There is a high prevalence of chronic hyponatremia in the elderly, frequently owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Recent reports have shown that even mild hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (µCT) and histomorphometric analyses indicated that hyponatremia markedly reduced both trabecular and cortical bone via increased bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild hyponatremia is associated with increased odds of osteoporosis (T-score –2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03–7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of diuretic use, history of smoking, and serum 25-hydroxyvitamin D [25(OH)D] levels. Our results represent the first demonstration that chronic hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that hyponatremia is associated with significantly increased odds of osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic hyponatremia. © 2010 American Society for Bone and Mineral Research

Rosiglitazone Activates Renal Sodium-and Water-Reabsorptive Pathways and Lowers Blood Pressure in Normal Rats

ABSTRACT Synthetic agonists of the peroxisomal proliferator-activated receptor subtype ␥ (PPAR-␥) are highly beneficial in the treatment of type II diabetes. However, they are also associated with fluid retention and edema, potentially serious side effects of unknown origin. These studies were designed to test the hypothesis that rosiglitazone (RGZ, PPAR-␥ agonist) may activate sodium-and water-reabsorptive processes in the kidney, possibly in response to a drop in mean arterial blood pressure (MAP), as well as directly through PPAR-␥. Targeted proteomics of the major renal sodium and water transporters and channel proteins was used to identify potentially regulated sites of renal sodium and water reabsorption. RGZ (47 or 94 mg/kg diet) was fed to male, Sprague-Dawley rats (ϳ270g) for 3 days. MAP, measured by radiotelemetry, was decreased significantly in rats fed either level of RGZ, relative to control rats. Delta MAP from baseline was Ϫ3.2 Ϯ 1.2 mm Hg in rats fed high-dose RGZ versus ϩ 3.4 Ϯ 0.8 for rats fed control diet. RGZ did not affect feed or water intake, but rats treated with high-dose RGZ had decreased urine volume (by 22%), sodium excretion (44%), kidney weight (9%), and creatinine clearance (35%). RGZ increased whole kidney protein abundance of the ␣-1 subunit of Na-K-ATPase, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the sodium hydrogen exchanger (NHE3), the aquaporins 2 and 3, and endothelial nitric-oxide synthase. We conclude that both increases in renal tubule transporter abundance and a decrease in glomerular filtration rate likely contribute to the RGZ-induced sodium retention

Glucose effects on gastric motility and tone evoked from the rat dorsal vagal complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66102/1/j.1469-7793.2001.t01-1-00141.x.pd

The efficacy of hypotonic and near-isotonic saline for parenteral fluid therapy given at low maintenance rate in preventing significant change in plasma sodium in post-operative pediatric patients: protocol for a prospective randomized non-blinded study

<p>Abstract</p> <p>Background</p> <p>Hyponatremia is the most frequent electrolyte abnormality observed in post-operative pediatric patients receiving intravenous maintenance fluid therapy. If plasma sodium concentration (p-Na⁺) declines to levels below 125 mmol/L in < 48 h, transient or permanent brain damage may occur. There is an intense debate as to whether the administered volume (full rate <it>vs. </it>restricted rate of infusion) and the composition of solutions used for parenteral maintenance fluid therapy (hypotonic <it>vs. </it>isotonic solutions) contribute to the development of hyponatremia. So far, there is no definitive pediatric data to support a particular choice of parenteral fluid for maintenance therapy in post-surgical patients.</p> <p>Methods/Design</p> <p>Our prospective randomized non-blinded study will be conducted in healthy children and adolescents aged 1 to 14 years who have been operated for acute appendicitis. Patients will be randomized either to intravenous hypotonic (0.23% or 0.40% sodium chloride in glucose, respectively) or near-isotonic (0.81% sodium chloride in glucose) solution given at approximately three-fourths of the average maintenance rate. The main outcome of interest from this study is to evaluate 24 h post-operatively whether differences in p-Na⁺between treatment groups are large enough to be of clinical relevance. In addition, water and electrolyte balance as well as regulatory hormones will be measured.</p> <p>Discussion</p> <p>This study will provide valuable information on the efficacy of hypotonic and near-isotonic fluid therapy in preventing a significant decrease in p-Na⁺. Finally, by means of careful electrolyte and water balance and by measuring regulatory hormones our results will also contribute to a better understanding of the physiopathology of post-operative changes in p-Na⁺in a population at risk for hyponatremia.</p> <p>Trial registration</p> <p>The protocol for this study is registered with the current controlled trials registry; registry number: <a href="http://www.controlled-trials.com/ISRCTN43896775">ISRCTN43896775</a>.</p

Diagnosis and management of hyponatraemia: AGREEing the guidelines

Hyponatraemia is a common electrolyte disorder associated with significant complications and controversies regarding its optimal management. Clinical practice guidelines and consensus statements have attempted to provide clinicians with evidence-based diagnostic and treatment strategies for hyponatraemia. Recently published guidance documents differ in their methods employed to review the quality of available evidence. Nagler et al. used the Appraisal of Guideline for Research and Evaluation (AGREE II) instrument in a systematic review of guidelines and consensus statements for the diagnosis and management of hyponatraemia. Nagler and colleagues highlighted the variability in methodological rigour applied to guideline development and inconsistencies between publications in relation to management of hyponatraemia (including the recommended rate of correction of a low serum sodium concentration). These differences could cause confusion for practising physicians managing patients with hyponatraemia.</p

Why Can't Rodents Vomit? A Comparative Behavioral, Anatomical, and Physiological Study

The vomiting (emetic) reflex is documented in numerous mammalian species, including primates and carnivores, yet laboratory rats and mice appear to lack this response. It is unclear whether these rodents do not vomit because of anatomical constraints (e.g., a relatively long abdominal esophagus) or lack of key neural circuits. Moreover, it is unknown whether laboratory rodents are representative of Rodentia with regards to this reflex. Here we conducted behavioral testing of members of all three major groups of Rodentia; mouse-related (rat, mouse, vole, beaver), Ctenohystrica (guinea pig, nutria), and squirrel-related (mountain beaver) species. Prototypical emetic agents, apomorphine (sc), veratrine (sc), and copper sulfate (ig), failed to produce either retching or vomiting in these species (although other behavioral effects, e.g., locomotion, were noted). These rodents also had anatomical constraints, which could limit the efficiency of vomiting should it be attempted, including reduced muscularity of the diaphragm and stomach geometry that is not well structured for moving contents towards the esophagus compared to species that can vomit (cat, ferret, and musk shrew). Lastly, an in situ brainstem preparation was used to make sensitive measures of mouth, esophagus, and shoulder muscular movements, and phrenic nerve activity-key features of emetic episodes. Laboratory mice and rats failed to display any of the common coordinated actions of these indices after typical emetic stimulation (resiniferatoxin and vagal afferent stimulation) compared to musk shrews. Overall the results suggest that the inability to vomit is a general property of Rodentia and that an absent brainstem neurological component is the most likely cause. The implications of these findings for the utility of rodents as models in the area of emesis research are discussed. © 2013 Horn et al