Three water restriction schedules used in rodent behavioral tasks transiently impair growth and differentially evoke a stress hormone response without causing dehydration

Water restriction is commonly used to motivate rodents to perform behavioral tasks; however, its effects on hydration and stress hormone levels are unknown. Here, we report daily body weight and bi-weekly packed red blood cell volume and corticosterone in adult male rats across 80 days for three commonly used water restriction schedules. We also assessed renal adaptation to water restriction using post-mortem histological evaluation of renal medulla. A control group received ad libitum water. After one week of water restriction, rats on all restriction schedules resumed similar levels of growth relative to the control group. Nominal hydration was observed, and water restriction did not drive renal adaptation. An intermittent restriction schedule was associated with an increase in corticosterone relative to the control group. Our results suggest that the water restriction schedules used here will maintain welfare in rats. However, intermittent restriction evokes a stress response which could affect behavioral and neurobiological results. Our results also suggest that stable motivation in behavioral tasks may only be achieved after one week of restriction.

Acetazolamide causes renal HCO3− wasting but inhibits ammoniagenesis and prevents the correction of metabolic acidosis by the kidney

Carbonic anhydrase (CAII) binds to the electrogenic basolateral Na+-[Formula: see text] cotransporter (NBCe1) and facilitates [Formula: see text] reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with the ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats treated with ACTZ to NH4Cl loading for up to 2 wk. The results indicated that ACTZ-treated rats exhibited a sustained metabolic acidosis for up to 2 wk, whereas in NH4Cl-loaded rats, metabolic acidosis was corrected within 2 wk of treatment. [Formula: see text] excretion increased by 10-fold in NH4Cl-loaded rats but only slightly (1.7-fold) in ACTZ-treated rats during the first week despite a similar degree of acidosis. Immunoblot experiments showed that the protein abundance of glutaminase (4-fold), glutamate dehydrogenase (6-fold), and SN1 (8-fold) increased significantly in NH4Cl-loaded rats but remained unchanged in ACTZ-treated rats. Na+/H+ exchanger 3 and NBCe1 proteins were upregulated in response to NH4Cl loading but not ACTZ treatment and were rather sharply downregulated after 2 wk of ACTZ treatment. ACTZ causes renal [Formula: see text] wasting and induces metabolic acidosis but inhibits the upregulation of glutamine transporter and ammoniagenic enzymes and thus suppresses ammonia synthesis and secretion in the proximal tubule, which prevented the correction of acidosis. This effect is likely mediated through the inhibition of the CA-NBCe1 metabolon complex, which results in cell alkalinization. During chronic ACTZ treatment, the downregulation of both NBCe1 and Na+/H+ exchanger 3, along with the inhibition of ammoniagenesis and [Formula: see text] generation, contributes to the maintenance of metabolic acidosis.

Acute Kidney Injury Impairs Postnatal Renal Adaptation and Increases Morbidity and Mortality in Very Low-Birth-Weight Infants

Objective This study aims to estimate the impact of acute kidney injury (AKI) on postnatal renal adaptation, morbidity, and mortality in very low-birth-weight (VLBW) infants. Design We conducted a retrospective study of 457 VLBW infants admitted to a tertiary level neonatal intensive care unit (NICU) between July 2009 and April 2015. We compared patient characteristics, risk factors, serum creatinine trends, and adverse outcomes in infants with and without AKI using multivariate logistic regression analysis. Results Incidence of AKI was 19.5%. On multivariate analysis, postnatal risk factors such as patent ductus arteriosus and vancomycin use were significantly associated with AKI. Infants with AKI had significantly higher mortality; 25/89 (28%) versus 15/368 (4%) (p < 0.001). Among survivors with AKI, bronchopulmonary dysplasia (BPD) was more prevalent (52.8 vs. 23.9%, p < 0.001), serum creatinine remained elevated for a longer duration and median length of stay extended by 38 days. Conclusion Presence of AKI was associated with impaired postnatal renal adaptation, BPD, significantly longer stay in the NICU and higher mortality.

Renal adaptation during hibernation

Hibernators periodically undergo profound physiological changes including dramatic reductions in metabolic, heart, and respiratory rates and core body temperature. This review discusses the effect of hypoperfusion and hypothermia observed during hibernation on glomerular filtration and renal plasma flow, as well as specific adaptations in renal architecture, vasculature, the renin-angiotensin system, and upregulation of possible protective mechanisms during the extreme conditions endured by hibernating mammals. Understanding the mechanisms of protection against organ injury during hibernation may provide insights into potential therapies for organ injury during cold storage and reimplantation during transplantation.