Effect Of Acute Uremia Research Articles

The effects of postoperative factors on serum thyroid hormones and rat liver nuclear 3,5,3'-triiodothyronine receptor concentrations in surgical models of uremia and regenerating liver.

We have determined the individual effects of postoperative fasting, surgical/anesthetic factors, acute uremia (AU), and regenerating liver (RL) on nucleoplasmic (NP; 0.15 M KCl-extractable) and chromatin-bound (CB; 0.4 M KCl-extractable) rat liver T3 receptors. AU and RL rats were studied 24 h after bilateral nephrectomy (blood urea nitrogen, 128 +/- 13 mg/dl) or two thirds hepatectomy, respectively. The effects of postoperative fasting were assessed by comparison of normal rats (N) with control rats (N6) pair-fed to match the caloric intake of the AU and RL rats. Surgical/anesthetic effects were determined by comparison of N6 rats with sham-operated pair-fed rats (S6). The effects of AU or RL were obtained by comparison with S6 controls. Changes in mean body weight attributable to fasting (N6-N), surgical/anesthetic effects (S6-N6), acute uremia (AU-S6), and regenerating liver (RL-S6) were: -17.3 (P less than 0.001), -4.0 (P = NS), -4.5 (P less than 0.05), and -1.0 g/24 h (P = NS), respectively. Changes in mean serum T4 (N, 5.3 +/- 1.3 micrograms/dl) were: -1.0 (P = NS), -0.6 (P = NS), -0.9 (P less than 0.05), and -1.0 micrograms/dl (P less than 0.05), respectively. Changes in mean serum T3 (N, 53 +/- 23 ng/dl) were: -8 (P = NS), -18 (P less than 0.05), -10 (P = NS), and -14 ng/dl (P less than 0.05), respectively. The NP and CB receptor pools of the AU and RL rats were not significantly different from those of age-matched N rats (NP, 25 +/- 5 fmol/mg DNA; CB, 405 +/- 134 fmol/mg DNA). Chronically uremic (CU) rats 2 weeks after five sixths nephrectomy (blood urea nitrogen, 36 +/- 2 mg/dl) did not exhibit significant change in their extractable receptor pools. Complete starvation for 24 h (NO) or 72 h (NOO) generally resulted in marked reductions in receptor concentrations compared to those in age-matched N rats fed ad libitum: NP pool (N, 31 +/- 17 fmol/mg DNA): NO-N, -40% (P = NS); NOO-N, -59% (P less than 0.01); CB pool (N, 303 +/- 105 fmol/mg DNA): NO-N, -19% (P less than 0.05); NOO-N, -41% (P less than 0.001). These studies indicate that severe AU, moderate CU, and LR have relatively little effect on solubilized rat liver nuclear receptor concentrations. In contrast, complete starvation is a potent depressant of both nuclear receptor pools. In the surgical models of AU and LR, postoperative fasting was the primary cause of weight loss.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic studies of adipose tissue in acute uremia

The effect of acute uremia on lipoprotein lipase (LPL) activity in rat adipose tissue and on the response of the isolated adipocytes to insulin was assessed. LPL activity in adipose tissue and in adipocytes of the uremic rats was decreased compared with values in sham-operated controls. Also, the adipocytes from uremic rats released significantly less than control amounts of LPL. In contrast, glucose oxidation by adipocytes isolated from uremic rats was not different from controls, and there was no difference in insulin binding or in insulin-stimulated glucose oxidation in the two groups. Triglyceride injected into the uremic rats was cleared at about half the control rate. Thus, the specific reduction in LPL activity in adipose tissue may be responsible, at least in part, for the defective removal of triglyceride. However, it is unlikely that the reduced LPL is due to a generalized toxic effect of uremia on adipose tissue since no significant alteration in insulin binding and glucose oxidation was found.

Effect of acute uremia on insulin removal by the isolated perfused rat liver and muscle

The effect of acute uremia on insulin removal by liver and muscle was investigated by measuring the extraction of porcine insulin during recycling perfusion of isolated liver and hindlimb from nephrectomized rats. Insulin removal by the liver was not affected by uremia, and hepatic extraction of insulin by normal and uremic livers averaged 38% at perfusate insulin concentrations ranging from 50 to 600 μU/ml. In contrast, insulin extraction by normal hindlimb averaged 13.4% at comparable insulin concentrations, and this was reduced to 4.3% as a result of acute uremia. A similar reduction in insulin extraction was noted when hindlimb from uremic animals was perfused with normal blood media or when normal hindlimb was perfused with uremic blood. These findings indicate that the efficiency of insulin removal by the liver is unaffected by uremia and is approximately threefold higher than that for hindlimb muscle. On the other hand, it is apparent that skeletal muscle, by virtue of its mass and relatively high blood flow, is also an important organ system for insulin removal. Furthermore, the data suggest that the 68% reduction in insulin extraction by hindlimb from uremic rats may contribute to the prolongation of insulin removal from plasma that is characteristic of patients with renal failure.

Effect of acute uremia on arginine metabolism and urea and guanidino acid production by perfused rat liver.

Since arginine is a precursor of urea and other guanidino derivatives, we have evaluated its metabolism in acute uremia using the isolated perfused rat liver. Female Sprague-Dawley rats underwent bilateral nephrectomy (n = 5) or sham operation (n = 5) 48 h prior to liver perfusion. Fifty microCi of L-[guanidino 14C] arginine and unlabelled arginine and aspartic acid were added to the recycling perfusate 15 min prior to liver perfusion. Perfusate concentrations of urea and other guanidino derivatives were measured with high-pressure liquid chromatography. After the initial 30 min of perfusion, net uptake of arginine was lower, and net release of guanidino-succinic acid (GSA) was higher in the livers of acutely uremic rats. Net release of urea was also higher in uremia but the results did not achieve statistical significance. In uremia, the percent conversion of 14C arginine to 14C urea was significantly higher (79 +/- 5 [SE]%) than in controls (58 +/- 7%). These results demonstrate increased GSA production by livers of acutely uremic rats and suggest that acute uremia may be associated with increased arginine utilization and increased production of urea.

Effect of acute uremia on triglyceride kinetics in the rat

Plasma triglyceride (TG) levels were elevated 24 hr after the production of acute uremia in rats. The effect of acute uremia on TG production rate was estimated by determining the rate of TG accumulation following Triton WR 1339 inhibition of lipoprotein removal, by measuring hepatic TG secretion rate during in situ liver perfusion, and by quantifying hepatocyte very low density lipoprotein content with the electron microscope. The results of all three of these approaches indicated that TG synthesis and secretion were decreased in acute uremia, suggesting that the associated increase in plasma TG levels had to result from a removal defect. This hypothesis was tested directly by injecting prelabeled very low density lipoprotein TG into acutely uremic and control rats, and measuring its rate of disappearance from plasma. The t 1 2 of removal in acutely uremic rats was found to be approximately twice that of control, confirming the hypothesis that the rise in plasma TG levels in acute uremia is due to a defect in removal of TG from plasma.

The effect of acute uremia on liver mitochondrial activity.

The effect of acute uremia on the liver mitochondrial activity was studied in Swiss albino mice subjected to complete urethral obstruction and sacrificed at different time intervals. The specific respiratory coefficient (measured as microliters of oxygen utilized per milligram of total proteins X 10(-1)) was similar in uremic and sham-operated control groups. The utilization of succinate as substrate was also similar in uremic and controls. There was a tendency for decreasing utilization of alpha-glutarate as substrate by the uremic group, particularly after 48 h of total urinary obstruction. There was no correlation between the retention of urea and the degree of mitochondrial respiratory inhibition.

Effect of acute uremia on various aspects of carbohydrate metabolism in dogs

Effect of acute uremia on various aspects of carbohydrate metabolism in dogs. Dogs were studied before and five days after diversion of both ureters into the vena cava. Mean (± sem) serum creatinine concentration (24 dogs) increased from 0.9 ± 0.03 to 15.3 ± 0.05 mg/100ml (P Effets de l'uremie aigue sur divers aspects du metabolisme des hydrates de carbone chez le chien. Des chiens ont ete etudies avant et cinq jours apres derivation des deux ureteres dans la veine cave. La creatininemie moyenne (±sem) de 24 chiens a augmente de 0,9 ± 0,03 mg/100 ml a 15,3 ± 0,05 mg/100 ml (P

Effect of acute uremia on pancreatic insulin stores in rats

The effect of acute uremia on stores of pancreatic insulin was examined. Four groups of rats were studied: nephrectomized rats on a special low nitrogen diet, sham-nephrectomized rats on the same diet, sham-nephrectomized rats on a normal diet, and normal rats on a normal diet. Uremia created by nephrectomy was allowed to continue for 6 days at which time animals were sacrificed. A period of 10 days of diet equilibration was done prior to nephrectomy. Total body weight, pancreas and liver weights declined in sham-operated and nephrectomized rats mostly attributable to the diet. In uremic rats, however, heart weights increased. Insulin expressed as U/g pancreas, total insulin per animal, U/100 g body weight, or as per cent of protein was significantly depressed in the uremic rats compared to sham-operated special diet controls.

The effects of acute uremia on plasma glucose, insulin and growth hormone in the rat

The effects of acute uremic syndrome upon plasma glucose, insulin and growth hormone were evaluated in the fasted rat 24 hours following bilateral nephrectomy. Appropriate control studies were instituted to correct for the non-specific effects of surgical intervention. The mean levels of plasma glucose, IRI and GH, as well as insulin to glucose ratio were significantly higher in the uremic animals than in the sham-operated controls. The fasting hyperglycemia in the presence of high levels of circulating IRI observed in the nephrectomized rats suggest impaired responsiveness of the peripheral tissues to the action of insulin. Since similar findings have been reported in chronic renal failure in the human, it is suggested that the acutely uremic rat might be employed as an experimental model for further elucidating the underlying mechanisms of glucose intolerance in uremia.

Effect of acute uremia on amino acid uptake and urea production by perfused rat liver.

Effect of acute uremia on amino acid uptake and urea production by perfused rat liver.