scholarly journals Antenatal betamethasone exposure alters renal responses to angiotensin-(1–7) in uninephrectomized adult male sheep

2012 ◽  
Vol 14 (4) ◽  
pp. 290-298 ◽  
Author(s):  
Jianli Bi ◽  
Stephen A Contag ◽  
Luke C Carey ◽  
Lijun Tang ◽  
Nancy K Valego ◽  
...  
2012 ◽  
Vol 302 (7) ◽  
pp. R868-R875 ◽  
Author(s):  
Reetu R. Singh ◽  
Karen M. Moritz ◽  
John F. Bertram ◽  
Kate M. Denton

We have previously shown that fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days) in male sheep results in a 30% nephron deficit, reduction in glomerular filtration rate (GFR) and renal blood flow, and elevation in arterial pressure at 6 mo of age. Furthermore, in response to an acute 0.9% saline load, sodium excretion was significantly delayed in uni-x animals leading us to speculate that tubuloglomerular feedback (TGF) activity was reset in uni-x animals. In the present study, we induced TGF blockade by furosemide administration (1.5 mg/kg iv over 90 min) and determined GFR, effective renal plasma flow, and urine and sodium excretion responses in 6-mo-old male sheep. In response to furosemide, a significant diuresis and natriuresis was observed in the sham group; however, the response was significantly delayed and reduced in uni-x animals (both, Ptreatment×time < 0.001). Cummulative urinary and sodium output was significantly less in the uni-x compared with the sham sheep (both, Ptreatment×time < 0.001). GFR was increased in the sham but not the uni-x sheep ( Ptreatment×time < 0.0001). In conclusion, the excretory response to furosemide was attenuated in the uni-x sheep, and this suggests a rightward resetting of the TGF operating point. The TGF mechanism is important in the fine tuning of sodium homeostasis and is likely a contributing factor for the dysfunction in sodium regulation we have previously observed in the uni-x animals.


1966 ◽  
Vol 8 (1) ◽  
pp. 155-156 ◽  
Author(s):  
Martyn H. Butterworth

The maintenance requirement for digestible organic matter of adult sheep has been derived by Wood and Capstick (1926) and more recently by Lang-lands, Corbett, McDonald and Pullar (1963) by means of regression analysis of data for feed intake, live-weight and live-weight gain.As data from digestibility trials carried out both in Trinidad and Venezuela were available, similar equations were derived for adult male sheep under tropical conditions. Groups of six adult male sheep were housed individually and total collections of faeces and urine were made for periods of 10 days after preliminary periods of 7 or 10 days. The quantity of forage offered was generally that which the individual sheep would eat without leaving a large residue. The results obtained in these trials and a more detailed description of the methods used have been described elsewhere (Butterworth, 1963; 1965). In all, 178 sets of data were used. Each set for an individual animal consisted of daily intake of digestible organic matter (D), the mean (W) of initial and final body weights, and daily change in weight (G) all in lb. Values of D and G were means obtained from the results for the 10-dayperiod. The value of G was subject to high error in determination as periods were short and measurement of weight change in ruminant animals over short periods is most unreliable (see for example, Lush, Christensen, Wilson and Black, 1928; Whiteman, Chambers, Loggins, Pope and Stephens, 1954). Mean values and ranges of the values were as follows: D=0·96 lb. (0·46–1·87 lb.), W=84·2 lb. (56·0–149·0 lb.) and G=0·02 lb. (-0·5-+0·5 lb.). The digestibility coefficients for the dry matter of the various forages used ranged from 47·3 to 68·0%.


2007 ◽  
Vol 192 (1) ◽  
pp. 87-97 ◽  
Author(s):  
M A Hyatt ◽  
G S Gopalakrishnan ◽  
J Bispham ◽  
S Gentili ◽  
I C McMillen ◽  
...  

The liver is a major metabolic and endocrine organ of critical importance in the regulation of growth and metabolism. Its function is determined by a complex interaction of nutritionally regulated counter-regulatory hormones. The extent to which hepatic endocrine sensitivity can be programed in utero and whether the resultant adaptations persist into adulthood is unknown and was therefore the subject of this study. Young adult male sheep born to mothers that were fed either a control diet (i.e.100% of total live weight-maintenance requirements) throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0 to 95 days gestation and thereafter 100% of requirements (taking into account increasing fetal mass) were entered into the study. All mothers gave birth normally at term, the singleton offspring were weaned at 16 weeks, and then reared at pasture until 3 years of age when their livers were sampled. NR offspring were of similar birth and body weights at 3 years of age when they had disproportionately smaller livers than controls. The abundance of mRNA for GH, prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the abundance of the mitochondrial protein voltage-dependent anion channel and the pro-apoptotic factor Bax were up regulated relative to controls. In conclusion, maternal nutrient restriction in early gestation results in adult offspring with smaller livers. This may be mediated by alterations in both hepatic mitogenic and apoptotic factors.


2011 ◽  
Vol 301 (2) ◽  
pp. F319-F326 ◽  
Author(s):  
Reetu R. Singh ◽  
Karen M. Moritz ◽  
E. Marelyn Wintour ◽  
Andrew J. Jefferies ◽  
Javed Iqbal ◽  
...  

Fetal uninephrectomy (uni-x) at 100 days of gestation results in compensatory nephrogenesis in the remaining kidney, resulting in a 30% reduction in total nephron number in male sheep. Recently, we showed that uni-x males at 6 mo of age have elevated arterial pressure, reduced renal blood flow (RBF), glomerular filtration rate (GFR), and low plasma renin levels (Singh R, Denton K, Bertram J, Jefferies A, Head G, Lombardo P, Schneider-Kolsky M, Moritz K. J Hypertens 27: 386–396, 2009; Singh R, Denton K, Jefferies A, Bertram J, Moritz K. Clin Sci (Lond) 118: 669–680, 2010). We hypothesized this was due to upregulation of the intrarenal renin-angiotensin system (RAS). In this study, renal responses to ANG II infusion and ANG II type 1 receptor (AT1R) blockade were examined in the same 6-mo-old male sheep. Uni-x animals had reduced levels of renal tissue and plasma renin and ANG II. Renal gene expression of renin, and gene and protein levels of AT1R and AT2R, were significantly lower in uni-x animals. In response to graded ANG II infusion, sham animals had the expected decrease in conscious RBF and GFR. Interestingly, the response was biphasic in uni-x sheep, with GFR initially decreasing, but then increasing at higher ANG II doses (34 ± 7%; Pgroup × treatment < 0.001), due to a paradoxical decrease in renal vascular resistance ( Pgroup × treatment < 0.001). In response to AT1R blockade, while GFR and RBF responded similarly between groups, there was a marked increase in sodium excretion in uni-x compared with sham sheep (209 ± 35 vs. 25 ± 12%; P < 0.001). In conclusion, in 6-mo-old male sheep born with a single kidney, these studies demonstrate that this is a low-renin form of hypertension, in which responses to ANG II are perturbed and the intrarenal RAS is downregulated.


2006 ◽  
Vol 40 (6) ◽  
pp. 988-989
Author(s):  
Julian P. Boullin ◽  
Arthur M. Yue ◽  
Jane K. Cleal ◽  
Lucy Braddick ◽  
Deborah Burrage ◽  
...  

Author(s):  
Itaru Watanabe ◽  
Dante G. Scarpelli

Acute thiamine deficiency was produced in mice by the administration of oxythiamine, a thiamine analogue, superimposed upon a thiamine deficient diet. Adult male Swiss mice (30 gm. B.W.) were fed with a thiamine deficient diet ad libitumand were injected with oxythiamine (170 mg/Kg B.W.) subcutaneously on days 4 and 10. On day 11, severe lassitude and anorexia developed, followed by death within 48 hours. The animals treated daily with subcutaneous injections of thiamine (300 μg/Kg B.W.) from day 11 through 15 were kept alive. Similarly, feeding with a diet containing thiamine (600 μg/Kg B.W./day) from day 9 through 17 reversed the condition. During this time period, no fatal illness occurred in the controls which were pair-fed with a thiamine deficient diet.The oxythiamine-treated mice showed a significant enlargement of the liver, which weighed approximately 1.5 times as much as that of the pair-fed controls. By light and electron microscopy, the hepatocytes were markedly swollen due to severe fatty change and swelling of the mitochondria.


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