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H. O. Garland

ABSTRACT

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 μg TRH over 30 min. The rapidity of the response may suggest a direct effect of TRH on the renal vascular system.

J. Endocr. (1987) 113,445–448

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J. Walker and H. O. Garland

ABSTRACT

Whole kidney and renal micropuncture techniques were used to investigate the effects of chronic prolactin treatment on kidney function in anaesthetized female rats. At the whole kidney level, glomerular filtration rate (GFR) and fluid reabsorption were both significantly (P<0·02) increased in the hormone-treated group. At the single nephron level, GFR and proximal fluid reabsorption were also increased (P<0·05) by prolactin treatment. Fractional reabsorption was also enhanced at the proximal tubular level in hormone-treated animals. Such changes in renal function are similar to those seen in rat pregnancy and cervically stimulated pseudopregnancy. Since circulating prolactin concentrations are increased in both reproductive states, the hormone may play an important role in establishing the characteristic renal changes seen therein.

J. Endocr. (1985) 107, 127–131

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A. B. Anwana and H. O. Garland

ABSTRACT

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 < 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 < 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.

Journal of Endocrinology (1991) 128, 333–337

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H. O. Garland, P. J. Harris and T. O. Morgan

ABSTRACT

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<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 resides 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<0·01).

Journal of Endocrinology (1991) 131, 373–380

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H O Garland, A G Forshaw and C P Sibley

Abstract

Hypercalciuria may be a contributory factor to the disturbed calcium homoeostasis seen in diabetic pregnant rats and their offspring. In diabetes, essential fatty acid metabolism is impaired. We have therefore investigated whether feeding a diet supplemented with essential fatty acids will ameliorate the hypercalciuria of diabetic pregnancy and improve reproductive performance.

Female rats were fed a standard rat diet, a fat-free diet plus evening primrose oil or a fat-free diet plus sunflower oil. They were injected with streptozotocin or vehicle and mated. Urine samples were analysed for calcium before injection and during gestation.

Term-pregnant diabetic rats fed evening primrose oil showed a 73% reduction in urinary calcium output compared with similar rats fed standard diet (P<0·001). The corresponding reduction was 44% in diabetic rats fed sunflower oil (P<0·001). A depletion of essential fatty acids in diabetes may therefore be associated with hypercalciuria; dietary supplementation, particularly with evening primrose oil, appears to correct the problem.

Diabetic pregnant rats fed evening primrose oil showed a significantly greater live fetal mass (85 ± 2 vs 33 ± 12 g; P<0·05) compared with similar rats fed standard diet. Such findings may imply a normalization of placental transport by essential fatty acids. Rats fed evening primrose, but not sunflower oil, also showed a reduced incidence of diabetes after streptozotocin injection compared with rats fed standard diet (63 vs 86%). Rats fed on evening primrose oil that did become diabetic were less hyperglycaemic than those on the standard diet (29 ± 2 vs 37 ± 2 mmol/l), suggesting that the oil may have anti-diabetic properties.

Journal of Endocrinology (1997) 153, 357–363

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T J Birdsey, S M Husain, H O Garland and C P Sibley

Abstract

The effect of maternal diabetes mellitus on renal calcium excretion in pregnant rats and their offspring has been examined in order to ascertain the role of the kidney in the disturbed calcium homeostasis of infants born to diabetic mothers. Diabetic pregnant (DP) rats exhibited severe hypercalciuria which greatly exceeded the urinary calcium losses (UCaV) in non-diabetic pregnant (CP) or non-pregnant diabetic (D) rats. Means ± s.e.m. for UCaV at day 21 (mmol/24 h) were: DP=1·12± 0·09 (n=7); CP=0·06±0·01 (n=7); D=0·63±0·06 (n=7) (P<0·001 DP vs CP and DP vs D). The profile for urinary calcium excretion in the three groups was different from that of other measured ions. The degree of natriuresis, for example, was comparable in DP and D rats at all stages studied. Although magnesium output was significantly greater in DP than D rats on days 14 and 21, this appeared to result from an additive effect of the magnesiuresis seen when pregnancy and diabetes were studied separately.

The marked renal calcium wasting of diabetic pregnancy will have implications for overall calcium balance in the mother. For example, an enhanced intestinal calcium absorption was seen in DP rats in the second half of gestation. Means ± s.e.m. for day 21 (mmol/24 h) were: DP=3·8±0·8 (n=7); CP=1·4±0·3 (n=7); D=1·6±0·3 (n=7) (P<0·05 DP vs CP and DP vs D). The hypercalciuria may also contribute to the disturbed calcium homeostasis of the neonate if it reduces the amount of calcium available for transfer to the fetus.

In contrast to their mothers, the offspring of DP rats did not show a raised UCaV compared with CP pups. Means ± s.e.m. at day 1 postpartum (nmol/2 h per pup) were: DP=47·2±15·7 (n=4 litters); CP=72·2±14·1 (n=7 litters) (not significant). Changes in neonatal renal function are therefore unlikely to contribute to their disturbed calcium balance. In fact, their slightly reduced urinary calcium output may be an attempt to compensate for their lowered total body calcium as reported elsewhere.

Journal of Endocrinology (1995) 145, 11–18

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H. O. Garland, J. C. Atherton, C. Baylis, M. R. A. Morgan and C. M. Milne

ABSTRACT

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.

J. Endocr. (1987) 113, 435–444