Phenotypic flexibility at the molecular and organismal level allows desert-dwelling rodents to cope with seasonal water availability.

We examined the phenotypic flexibility of field urine osmolality (Uosm) in response to seasonal rainfall and the experimental expression of renal aquaporins (AQPs) in the leaf-eared mouse Phyllotis darwini, a South American desert-dwelling rodent, through an integrative study at both the cellular and the organismal level. Field Uosm was higher in summer than in winter. Fall and winter Uosm were not significantly different. During a rainy year, winter Uosm was 2,140 +/- 82.3 mOsm kg(-1); the corresponding value in a dry year was 2,569 +/- 61.3 mOsm kg(-1). During the summer, the mean Uosm in a rainy year was 3,321 +/- 71.5 mOsm kg(-1), and in a dry year it was 3,604 +/- 107.2 mOsm kg(-1). The distribution of AQP-2, AQP-3, and AQP-4 was similar to that described for mouse and rat kidneys and confined to principal cells in cortex and inner medullary collecting-duct cells. AQP-4 immunoreactivity was unaltered by the state of water balance. Relative to water loading, dehydration induced an increase in AQP-2 immunoreactivity and protein abundance. Although more discrete, AQP-3 immunolabeling was also increased by dehydration. We now reveal how the integration of flexible renal mechanisms acting at the cellular and organismal level allow a small desert-dwelling mammal to cope with seasonal and yearly (El Nino) water availability in its semiarid habitat.

Renal physiology of two southern African Mastomys species (Rodentia: Muridae): a salt-loading experiment to assess concentrating ability.

Aspects of renal physiology were examined to test the hypothesis that two cryptic species of the genus Mastomys (Mastomys natalensis and Mastomys coucha) are geographically separated by differences in aridity tolerance. Laboratory-bred females of each species were subjected to different levels of salinity in their water source (distilled water, 0.9% NaCl, and 1.5% NaCl; 10 conspecifics in each group) from weaning until sexual maturity. Individuals of the two species exhibited similar rates of water consumption and urine production. The salinity treatments caused sodium diuresis in both species, evident in increased urine volume, decreased osmolality and increased osmotic output. Urine concentration, kidney mass and kidney relative medullary area (RMA) did not differ between species. The results of our study do not support the hypothesis that differences in osmoregulatory ability separate these two cryptic species. Nor do they support the use of salt loading to elicit maximum urine concentrations in mammals.

NMR spectroscopy based metabonomic studies on the comparative biochemistry of the kidney and urine of the bank vole (Clethrionomys glareolus), wood mouse (Apodemus sylvaticus), white toothed shrew (Crocidura suaveolens) and the laboratory rat.

The metabolic profiles of three wild mammals that vary in their trophic strategies, the herbivorous bank vole (Clethrionomys glareolus), the granivorous wood mouse (Apodemus sylvaticus), and the insectivorous white-toothed shrew (Crocidura suaveolens), were compared with that of a widely used strain of laboratory rat (Sprague Dawley). In conjunction with NMR spectroscopic investigations into the urine and blood plasma composition for these mammals, high resolution magic angle spinning (HRMAS) 1H-nuclear magnetic resonance (NMR) spectroscopy was applied to investigate the composition of intact kidney samples. Adaptation to natural diet affects both renal metabolism and urinary profiles, and while these techniques have been used to study the metabolism of the laboratory rat little is known about wild small mammals. The species were readily separated by their urinary profiles using either crude metabolite ratios or statistical pattern recognition. Bank vole urine contained higher concentrations of aromatic amino acids compared with the other small mammals, while the laboratory rats produced relatively more hippurate. HRMAS 1H-NMR demonstrated striking differences in both lipid concentration and composition between the wild mammals and Sprague Dawley rats. Bank voles contained high concentrations of the aromatic amino acids phenylalanine, tyrosine and tryptophan in all tissue and biofluids studied. This study demonstrates the analytical power of combined NMR techniques for the study of inter-species metabolism and further demonstrates that metabolic data acquired on laboratory animals cannot be extended to wild species.

Comparative studies on the nephrotoxicity of 2-bromoethanamine hydrobromide in the Fischer 344 rat and the multimammate desert mouse (Mastomys natalensis).

Renal papillary necrosis (RPN) was induced in Fischer 344 (F344) rats (n = 4) using 2-bromoethanamine hydrobromide (BEA) dosed at 150 mg/kg, and in multimammate desert mice (Mastomys natalensis) at 150 and 250 mg/kg (n = 4 per group). Control rats and Mastomys were dosed with 0.9% saline (n = 4 per group). Urine was collected at regular intervals for up to 4 days post-dosing and analysed for low MW metabolites using high resolution 1H NMR spectroscopy. The urinary activity of lactate dehydrogenase, gamma-glutamyl transpeptidase and alkaline phosphatase was determined using conventional biochemical assays. On termination, histopathological examination of papillae was performed showing the development of extensive lesions in F344 rats at 150 mg/kg BEA. Mastomys appeared much more resistant to BEA and showed normal renal histology at 150 mg/kg and patchy lesions at 250 mg/kg BEA. Enzyme analysis of control urine showed F344 rats to have > 1000% higher gamma-glutamyl transpeptidase activity than Mastomys. 1H NMR spectroscopic analysis showed that BEA caused a substantial decrease in urinary concentrations of succinate and citrate (0-24 h p.d.) and an increase in creatine (0-96 h p.d.) in both animal models. A decrease in the urinary concentration of 2-oxoglutarate with a subsequent increase by 72-96 h p.d. was also noted in both animal models. Glutaric and adipic aciduria were also induced in both F344 rats and Mastomys 0-24 h post-BEA treatment, indicative of an enzyme deficiency in the acyl CoA dehydrogenases. Urinary taurine levels were elevated in Mastomys following the administration of BEA, indicating some degree of liver toxicity. Urinary taurine was not elevated in F344 rats following BEA administration, demonstrating further species difference in BEA toxicity.

Identification of crystalline allantoin in the urine of African Cricetidae (Rodentia) and its role in their water economy.

All eleven cricetid species, examined in this investigation, produced an off-white crystalline precipitate in their urine when deprived of water, whereas not one murid examined did so. This crystalline compound was identified as allantoin, a common end product of purine catabolism. The quantity found in the solid precipitate alone accounted for 47% of the total nitrogen excreted and was approximately 14 times greater than the predicted quantity of allantoin from purine degradation. It appears that there is a shift in nitrogen excretion from urea to allantoin in the Cricetidae. Water-deprived cricetids had higher urine osmolalities, urea concentrations and lower daily percentage body water turnovers than the murids. This can be explained by the substantial water savings associated with excreting solid allantoin. The discrepancy in the mode of nitrogen excretion between the two families inhabiting the Namib Desert can be attributed to their different evolutionary histories, the Cricetidae being pre-adapted for survival in deserts.

The ecophysiological significance of calcium bicarbonate in the urine of subterranean rodents: testing a hypothesis.

1. A comparative study of calcium and bicarbonate in the urine was carried out on the subterranean mole rat Cryptomys hottenttus and the terrestrial vlei rat Otomys irroratus. 2. The two species were kept on two different diets; carrots, a high calcium diet (41 mg/ 100 kg) or potatoes, a low calcium diet (14 mg/ 100g). 3. The results show that the urine of the mole rat contained high values of calcium bicarbonate on either diet. 4. The urine of the vlei rat showed high values of calcium bicarbonate only when kept on the high calcium diet. 5. From these results we assume that in subterranean rodents excretion of calcium bicarbonate is an adaptive mechanism to unload CO2 without increasing its concentration in the hypercapnic environment.

Method for the microassay of endogenous creatinine in blood and urine of small murid rodents.

The estimation of endogenous creatinine clearance yields information useful to the renal physiologist without the need to introduce a marker compound. The method has been limited in its application to mammalian species of bodyweight 200 g and above due to the blood sample size required. A modification is described whereby this procedure may be applied to animals of bodyweight as low as 25 g. Use of this microassay is illustrated in an investigation of the effect of salt and urea loading on renal function in an Australian desert mouse, Notomys alexis.