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H O Garland

Publications and source records attributed to H O Garland.

18 recordsLinked to original sources
PubMed1992

Gentamicin-induced hypercalciuria in the rat: assessment of nephron site involved.

Two independent techniques were used in anesthetized rats in an attempt to locate the nephron site of the reduced tubular calcium reabsorption accompanying acute gentamicin infusion. The first technique was that of lithium clearance used to assess proximal sodium (and secondarily calcium) handling. Observations that lithium clearance was comparable in control and gentamicin-treated animals (1.83 +/- 0.39 vs. 1.46 +/- 0.14 ml.min-1 for first experimental period) suggests a lack of proximal effect of the drug. The second technique was that of tracer microinjection whereby superficial nephrons were injected with 45Ca and tubule calcium transport was assessed from the recovery of radioactivity in the final urine. 45Ca recovery values from distal microinjections were comparable in control and gentamicin-treated groups (81.1 +/- 2.0 vs. 77.7 +/- 4.6%). However, 45Ca recovery values from proximal microinjections were significantly higher in the gentamicin group (9.4 +/- 1.0 vs. 3.5 +/- 0.8%; P < .001). These data suggest that the effects of gentamicin on renal calcium handling are mediated at a nephron site proximal to the distal tubule (i.e., loop of Henle or proximal tubule itself). Closer examination of individual proximal micropuncture data may point to an effect occurring predominantly in the pars recta of the proximal tubule or loop of Henle. Taken together, the results of both parts of the present study suggest that the early physiological effects of gentamicin on the kidney occur in a different nephron segment from any subsequent nephrotoxicity.

Animals↗
PubMed1992

New experimental data on the relationship between diabetes mellitus and magnesium.

Diabetes mellitus is the most frequent chronic disease associated with secondary magnesium deficit. Hypomagnesaemia is a central feature of the deficit, which is often reported in experimental and clinical forms of the disease. In diabetic rats as in man, plasma magnesium concentrations may correlate inversely with the degree of hyperglycaemia. The duration of the disease also appears to be relevant. The hypomagnesaemia of diabetes might be expected to affect intracellular concentrations of the ion. However, although some animal and clinical studies have reported subnormal magnesium concentrations in blood cells, bone, and soft tissues of diabetics, the relationship between plasma magnesium concentration and intracellular level of the ion is inconsistent. Clinical studies have speculated on a potential link between the magnesium deficit of diabetes and several diabetic complications, including cardiovascular problems and retinopathy. Recent experimental studies are largely supportive of such a link; myocardial disorders associated with magnesium deficiency have been reported in diabetic mice and rabbits. It is possible that a common mechanism involving magnesium may be responsible for some of the diverse complications of diabetes. The aetiology of hypomagnesaemia in diabetes is complex. Nevertheless, plasma magnesium concentrations are ultimately determined by four processes: intake, gastrointestinal absorption, redistribution within body pools, and urinary excretion. This review considers in turn the potential role of each of these processes in the development of diabetic hypomagnesaemia. Both experimental and clinical studies suggest that hypermagnesiuria may be the major factor involved. Recent animal studies have described a specific renal tubular magnesium defect in diabetes, which, together with the osmotic diuresis, is responsible for large magnesium losses. The precise cause of the defect is unknown, but it may relate to the prolonged hyperglycaemia, insulinopenia, disturbance of phosphate metabolism, or other hormonal changes which characterize the disease.

Animals↗
PubMed1992

An investigation of the acute effect of gentamicin on the renal handling of electrolytes in the rat.

Standard renal clearance techniques were used to investigate the acute effects of gentamicin on renal electrolyte handling in anesthetized rats. Data were obtained before substantial changes in tubular integrity would be expected to occur, thus permitting a distinction between the actions of the drug per se and renal changes resulting from underlying tubular damage. Infusion of gentamicin over a 3-hr period resulted in an immediate and sustained calciuresis and magnesiuresis, with no significant change in the renal clearance of sodium or potassium. Within 60 min of the onset of drug infusion at 0.28 mg/kg/min, renal calcium clearance (ml/min) increased from 0.095 +/- 0.013 to 0.210 +/- 0.016 (P less than .001) and renal magnesium clearance (ml/min) increased from 0.538 +/- 0.059 to 0.662 +/- 0.053 (P less than .01). Because it was subsequently shown that infusion of gentamicin did not alter glomerular filtration rate, it is clear that both responses resulted from a reduced tubular reabsorption of the respective ions; they were rapidly reversible when gentamicin infusion ceased. A higher dose of gentamicin (0.56 mg/kg/min for 3 hr) also significantly decreased plasma magnesium concentrations (0.40 +/- 0.01 vs. 0.49 +/- 0.02 mmol/l, treated vs. control; P less than .01). Gentamicin-induced changes in the renal handling of calcium and magnesium, therefore, occur independently of and before the development of nephrotoxicity. They may be at least partially responsible for the alteration in electrolyte homeostasis seen in humans during aminoglycoside treatment (e.g., hypomagnesemia). It is interesting to speculate on the possibility that they may also in some way contribute to the subsequent cellular injury that is known to occur with prolonged use of gentamicin.

Animals↗
PubMed1991

Intracellular dehydration in the rat made diabetic with streptozotocin: effects of infusion.

Metabolic and isotopic dilution techniques were used to investigate fluid balance and fluid volumes in rats made diabetic with streptozotocin before and after infusion. Uninfused diabetic rats had significantly (P less than 0.01) lower total body water than controls (57.7 +/- 2.2 vs 65.7 +/- 1.4% (S.E.M.) fat free mass). This was due exclusively to a significantly (P less than 0.001) reduced intracellular fluid volume (38.2 +/- 1.5 vs 45.4 +/- 1.4% fat free mass). Metabolic studies over the preceding 2 weeks showed that the fluid deficit in the diabetic group had resulted from a failure of the rats to increase their fluid intake to the same extent as their combined fluid losses. A 4-h saline infusion halved the fluid deficit in diabetic animals. The retained fluid was used to restore intracellular fluid volume which became comparable in diabetic and control rats (47.2 +/- 2.0 vs 46.4 +/- 1.0% fat free mass). The retention of infusate by diabetic animals to counteract their intracellular dehydration may partly explain the reduced urine output reported elsewhere in infused anaesthetized diabetic rats.

Animals↗
PubMed1991

Calcium transport in the proximal convoluted tubule and loop of Henle of rats made diabetic with streptozotocin.

In-vivo microperfusion was used to localize the reabsorptive defect responsible for the hypercalciuria of diabetes mellitus and to investigate possible causative factors. Unidirectional proximal calcium absorption was not significantly different in rats made diabetic with streptozotocin compared with controls, providing evidence against the involvement of this nephron segment in the phenomenon. Calcium absorption by the loop of Henle, was however, significantly (P less than 0.01) lower in diabetic animals (32.1 +/- 1.2 vs 40.4 +/- 0.6 pmol/min). Based on our knowledge of calcium movements within the loop, it is likely that the reabsorptive defect residues within the thick ascending limb. The calcium lesion was found to be independent of acute changes in intraluminal glucose concentration and could not be corrected by acute insulin treatment. The study also provides new information on the relationship between intratubular glucose and fluid movements in the rat nephron. In diabetic rats a proximal perfusate containing 30 mmol glucose/l resulted in fluid absorption comparable with that seen in control rats perfused with 5 mmol glucose/l. However, intraluminal glucose had a stimulatory effect on fluid absorption in the loop of Henle of diabetic rats (10.7 +/- 0.5 vs 7.9 +/- 0.4 nl/min; P less than 0.01).

Absorption↗
PubMed1990

Renal calcium and magnesium handling in experimental diabetes mellitus in the rat.

Metabolic and renal clearance techniques were used to examine kidney function in conscious and anesthetised streptozotocin diabetic rats. All diabetics showed an enhanced calcium and magnesium excretion compared to controls. However, the renal handling of these ions in relation to other electrolytes varied with different experiments. In non-infused conscious rats, the excretion of all ions was higher in diabetics, but the increased output of Ca2+ and Mg2+ was far greater than that of other electrolytes. In infused anesthetised diabetics only the outputs of Ca2+ and Mg2+ were significantly raised. This resulted from a significant reduction in the tubular reabsorption of both ions (% Ca2+ reabsorption: Controls 97.0 +/- 0.5; Diabetics 86.1 +/- 2.1; p less than 0.001). Insulin treatment reversed these changes. Major differences therefore exist in the renal handling of Ca2+ and Mg2+ in control and diabetic kidneys. Such differences do not simply parallel changes in the handling of other ions, and thus represent specific Ca2+ and Mg2+ lesions. Anesthetised infused diabetic rats also showed a reduced glomerular filtration rate and urine output compared to controls. Such differences may relate to an altered fluid balance in the two groups, different responses to surgery and anesthesia, or the degree of hyperglycemia in diabetic animals.

Animals↗
PubMed1989

A comparison of the effects of oral and intravenous glucose administration on renal calcium excretion in the rat.

Standard renal clearance techniques were used to compare the effects of oral and intravenous glucose administration on renal calcium handling in the rat. A significant (P less than 0.01) calciuric response was evident in both groups following glucose loading. The maximal effect in the oral group, however, was slightly delayed. The increased urinary calcium excretion in both groups was the result of a reduction in fractional calcium reabsorption. The filtered load of calcium was unchanged. The response was also independent of changes in urinary sodium output, urine flow rate and glycosuria. The role of insulin in the response remains unclear.

Administration, Oral↗
PubMed1988

Effects of D-glucose, 2-deoxy-D-glucose and D-xylose on renal function in the rat.

1. Standard renal clearance techniques were used to investigate the effects of 2.5, 5 and 10% D-glucose, 2.5% 2-deoxy-D-glucose and 2.5% D-xylose on kidney function in male rats. 2. There was no consistent effect of D-glucose on urinary sodium output except with 10% D-glucose, where sodium excretion was raised compared to controls. 3. An increased urinary calcium output was seen in all D-glucose-infused rats compared to controls. Values obtained for 2.5, 5 and 10% glucose were respectively 32, 61 and 58% above control data. Neither 2-deoxy-D-glucose nor D-xylose produced a calciuresis. 4. The increased urinary calcium excretion in D-glucose rats was the result of a reduction in fractional calcium reabsorption. Glomerular filtration rate (GFR) was unchanged. It was not dependent upon glycosuria or a diuresis.

Absorption↗
PubMed1987

Altered renal function in chronically hyperprolactinaemic rats.

1. Standard renal clearance techniques were used to investigate the effects of chronic hyperprolactinaemia on kidney function in male, female and ovariectomized female rats. 2. All hyperprolactinaemic rats showed a significantly increased glomerular filtration rate (G.F.R.) compared to controls. Values were (microliter min-1) 2738 +/- 146 vs. 2299 +/- 99 for males (P less than 0.05), 2236 +/- 79 vs. 1865 +/- 74 for females (P less than 0.01) and 2200 +/- 76 vs. 1941 +/- 62 for ovariectomized females (P less than 0.05). 3. Hyperprolactinaemic rats in all groups also showed a significant increase in absolute tubular reabsorption of water, sodium and chloride compared to their respective controls. Increases here averaged 19%. 4. There was a significantly greater fractional tubular reabsorption of fluid and solutes in hyperprolactinaemic male rats compared to controls. Values were (%) 92.9 +/- 0.6 vs. 90.3 +/- 0.7 for water, 93.0 +/- 0.4 vs. 91.0 +/- 0.6 for sodium and 89.9 +/- 0.7 vs. 86.5 +/- 0.9 for chloride. In each case P less than 0.05. 5. These results imply an osmoregulatory role for prolactin which is not specific to pregnancy or related female reproductive states.

Absorption↗
PubMed1987

Hormone profiles for progesterone, oestradiol, prolactin, plasma renin activity, aldosterone and corticosterone during pregnancy and pseudopregnancy in two strains of rat: correlation with renal studies.

Plasma samples were obtained throughout pregnancy and pseudopregnancy from Sprague-Dawley (SD) rats and during pregnancy from rats of the Munich Wistar (MW) strain. The concentrations of progesterone, oestradiol, prolactin, plasma renin activity (PRA), aldosterone and corticosterone were measured by radioimmunoassay to establish hormonal profiles in the two strains of rat. Circulating progesterone concentrations in both strains of rat were significantly higher during pregnancy than in virgin controls, except at term in the SD group. The hormonal pattern for pseudopregnancy was similar to that of the first half of pregnancy. Oestradiol concentrations were similar to, or lower than, those in virgin controls throughout pseudopregnancy and for the first 2 weeks of pregnancy in both strains of rat. Increased concentrations of steroid were seen only in the pregnant groups towards term. In SD rats, highest prolactin concentrations were apparent during the first half of pregnancy and pseudopregnancy, and at term in the pregnant group. Pregnant MW rats showed a different profile for this hormone, with low levels throughout pregnancy except at term. In all groups PRA rose to a peak at day 9 and decreased to day 16. Pregnant SD rats also showed a significant increase at term. Aldosterone concentrations were significantly increased at several stages of pregnancy in both strains of rat, particularly during the second half of gestation. Pseudopregnant animals showed a different hormone profile, with no significant changes until day 16 when lower concentrations were recorded. There was little variation in the circulating corticosterone concentration except in pregnant rats at term when levels fell. These findings are discussed in relation to the known renal changes of pregnancy and pseudopregnancy.

Aldosterone↗
PubMed1987

Effects of thyrotrophin-releasing hormone on renal function in the rat.

Standard renal clearance techniques were used to investigate the acute effects of TRH on kidney function in anaesthetized rats. A significant reduction in salt and water outputs, glomerular filtration rate and renal plasma flow was produced within 10 min of infusion of 12 micrograms TRH over 30 min. The rapidity of the response may suggest a direct effect of TRH on the renal vascular system.

Animals↗
PubMed1986

Kidney function in rats with corticomedullary nephrocalcinosis: effects of alterations in dietary calcium and magnesium.

Single-nephron and whole-kidney function were studied in female rats with corticomedullary nephrocalcinosis, and in animals where the lesion had been prevented either by a dietary magnesium supplement or by using a diet with a calcium:phosphorus ratio in excess of 1. At the single-nephron level, rats with nephrocalcinosis had prolonged tubular fluid transit times. Proximal transit time was 19.42 +/- 1.98 (mean +/- S.E. of mean) vs. 11.58 +/- 0.19 s for controls; distal transit time was 62.64 +/- 9.16 vs. 31.50 +/- 1.03 s for controls. Although single-nephron function is altered in nephrocalcinosis, data obtained from rats in metabolism cages indicate that whole-kidney function is largely unaffected by the lesion.

Animals↗
PubMed1979

Computerised image analysis of split-drop micropuncture data.

A technique is described for rapid and reproducible analysis of split-drop micropuncture sequences recorded on film. Automatic identification of the droplet menisci in each cine frame, and subsequent evaluation is performed by a computerised T.V. image analysis system. In comparison with a more conventional technique, the improvement in reproducibility of the analysis is achieved without loss of accuracy and is accompanied by a three fold increase in speed.

Animals↗
PubMed1975

Micropuncture study of the renal responses of the urodele amphibian Necturus maculosus to injections of arginine vasotocin and an anti-aldosterone compound.

1. Necturus maculosus kidney function has been examined using standard clearance techniques and renal tubular micropuncture methodology. 2. Throughout, cyanocobalamin (vitamin B12) has been used to monitor glomerular filtration rate (GFR) and tubular water movements. It was established that this substance was handled by the Necturus kidney in a similar manner to inulin. It can be readily analysed, together with renal electrolytes, by electron microprobe techniques. 3. Profiles of transtubular gradients (TF:P ratios) along the nephron were established for osmolarity, sodium, potassium, calcium and cobalt (of cyanocobalamin). 4. Ureteral urine is always hyposmotic with respect to plasma and the site of dilution of the plasma ultrafiltrate is within the distal segment. 5. Up to 30% of the filtrate is isosmotically reabsorbed along the proximal tubule; the tubular fluid:plasma ratio for osmolarity and sodium is around 1, and the TF:P for cobalt of cyanocobalamin is about 1.4 by the end of this segment. 6. The renal effects of the neurohypophysial hormone arginine vasotocin (AVT) and an aldosterone antagonist (SC14266; Soldactone) have been examined. 7. AVT was consistently antidiuretic causing both a decreased GFR and an enhanced distal tubular reabsorption of water. 8. SC14266 also increased distal tubular reabsorption of water. Such an effect differs from that found in higher vertebrates, and may indicate a "glucocorticoid-type" of renal action for aldosterone in amphibians.

Aldosterone↗