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Biomedical subjects

D E Oken

Publications and source records attributed to D E Oken.

At least 37 records · Page 2Linked to original sources
PubMed1980

Renal function and mercury level in rats with mercuric chloride nephrotoxicity.

The levels of Hg++ in different subcellular compartments of rat kidney cortex were determined after a single subcutaneous injection of 203HgCl2, 4.7 mg/kg body weight. By 30 min after injection, cortical Hg++ level was 46.3 +/- 6.8 micrograms/g protein. A maximal cortical Hg++ value of 429 +/- 49 micrograms/g protein was reached 4 h after injection. Hg++ associated with the brush border membrane showed a progressive increase during the first 15 h after injection, but at each time interval was significantly less than cortical Hg++. The 45-hour values for cortex and brush border were equivalent. No evidence for the presence in plasma or kidney tissue of free Hg++ was obtained. Saline loading protected animals against the development of renal failure and resulted in significant lowering of cortical Hg++ levels without an effect on blood Hg++ concentration.

Acute Kidney Injury↗
PubMed1978

Simultaneous quantitation of twenty-two amino acids in nanolitre samples of biological fluid.

The technique of thin-layer chromatography and 14C-dansylation has been used for simultaneous measurements of 22 individual amino acids, taurine, serotonin, and gamma-aminobutyric acid in nanolitre samples of glomerular and renal tubule fluid. Standard curves of each amino acid mixture containing all the others showed excellent linearity at amounts ranging from 5.7.10(-13) to 1.45.10(-11) mole (regression coefficients all greater than 0.95). With careful standardization of dansylation conditions, the technique permits highly reproducible measurement of less than 1 pmole of an amino acid.

Amino Acids↗
PubMed1978

Micropuncture studies of the transport of individual amino acids by the Necturus proximal tubule.

Absorption of amino acids by the necturus proximal tubules was measured under free-flow conditions The coexistence of proximal tubular amino acid influx was determined by infusing saline into tubular lumens by the stopped-flow microperfusion technique. Under free-flow conditions, fractional absorption of individual amino acids ranged from 0.30 +/- 0.18 (glutamic acid) to 0.96 +/- 0.02 (proline), with 14 of 19 values greater than 0.75. The transport avidity for a given amino acid bore no relationship to its molecular weight, transport class, or plasma concentration. The values obtained for tubular fluid/plasma (TF/P) were very comparable to those reported for the rat. In stopped-flow microperfusion experiments, samples of isotonic saline residing in tubule lumens for 20 min were found to contain all the amino acids present in plasma (filtrate). The concentrations of all except the acidic anionic pair, glutamic acid and aspartic acid, were remarkably similar to those obtained by collection of end proximal samples in free-flow studies. The very high concentrations of the acidic amino acids may reflect their passive distribution across the luminal cell membrane, active absorption having been impaired by the absence of some substance normally present in glomerular filtrate.

Amino Acids↗
PubMed1978

Renin release and the refractoriness to acute renal failure of rats recovering from prior renal failure.

Renin substrate concentrations and the release of renin in response to the rapid removal of 15 ml/kg weight blood or subcutaneous administration of 500 microgram/kg body weight isoproterenol were measured in control rats and animals recovering from prior myohemoglobinuric acute renal failure (recovery rats). Blood for these assayas was drawn from chronically implanted aortic catheters, obviating the need for animal handling and anesthesia. Baseline plasma renin titers of recovery rats were modestly elevated but renin substrate concentrations were the same as in controls. Hemorrhage produced equivalent changes in blood pressure and plasma renin titer in the two groups. Isoproternol injection in recovery rats caused a somewhat greater blood pressure fall and almost twice the rise in plasma renin concentration observed in control rats. The marked resistance of recovery animals to a second bout of acute renal failure thus cannot be attributed to impaired renin release or inadequate plasma renin substrate.

Acute Kidney Injury↗
PubMed1978

The pathogenetic significance of intravascular coagulation in experimental acute renal failure.

Serum and urine fibrin(ogen) degradation products (FDP), FDP clearances, and serum urea nitrogen (SUN) concentrations of rats challenged with glycerol-induced myohemoglobinuria were measured serially over a period of 4 days. The results obtained in animals that developed acute renal failure (ARF) were compared with those obtained in rats made refractory to renal failure by long-term salt loading or recent recovery from prior renal failure. Only the rats susceptible to ARF experienced a major rise in serum FDP concentration. Urine FDP excretion rose most markedly in the same rats but, being elevated in all groups. showed the utilization of fibrinogen whether serum FDP values increased or not. The results obtained might reflect differences in the degree of intravascular coagulation which are pathogenetically important. It is possible, however, that increased serum FDP concentrations found exclusively in rats with ARF are the results rather than the cause of impaired filtration, and that reduced tubular absorption may at least partly account for the high urinary FDP excretion observed in this model of experimental acute renal failure.

Acute Kidney Injury↗
PubMed1977

Micropuncture studies of the filtration and absorption of albumin by nephrotic rats.

The proximal tubular fluid albumin concentration of rats with immunologically induced nephrotic syndrome rose from 0.60 +/- 0.11 (SEM) mg/100 ml to 7.42 to 0.87 mg/100 ml. The glomerular filtration rate (GFR) was slightly depressed (P less than 0.001) and fractional water absorption unchanged (P greater than 0.45). Urinary albumin excretion rose from 0.18 +/- 0.03 (SEM) mg/100 g of body wt/24 hr to 78.5 +/- 39.5 mg/100 g/100 g of body wt/24 hr (P less than 0.001). The concentration of albumin in glomerular filtrate, calculated as the product of proximal tubular albumin concentration and fractional water absorption (4.53 +/- 0.60 mg [SEM]/100 ml), equalled that calculated from urine albumin concentration and whole kidney water absorption (4.14 +/- 0.84 mg/100 ml, P greater than 0.30). The data are interpreted to reflect a significant increase in filtered albumin and only a modest (if any) tubular albumin absorption in this study. Thus, the concept that tubular absorption plays a major role in the catabolism of albumin and the genesis of hypoalbuminemia in the nephrotic syndrome could not be confirmed.

Absorption↗
PubMed1977

Normal renocortical blood flow in experimental acute renal failure.

Renal cortical blood flow of rats with postischemic, myohemoglobinuric, and mercury-induced acute renal failure was measured by the hydrogen washout technique using implanted platinum electrodes. Total renal blood flow was determined by venous cannulation in separate series of rats. The values obtained with the two methods were in excellent qualitative agreement (r=0.99, P less than 0.001), although venous cannulation gave values that were constantly lower than those calculated for whole kidney from the cortical flow rate and assumed cortical mass. Myohemoglobinuria produced by glycerol injection caused cortical blood flow to fall from a control value of 7.37+/-0.23 (SEM) ml/min X g of cortex to approximately one-half that value for four hours after injection (P less than 0.001). Flow rates 12 and 24 hr after glycerol injection were 85% (P less than 0.001) and 90% (P less than 0.05) of control, respectively. Cortical flow was reduced to 5.49+/-0.39 (SEM) ml/min X g of cortex four hours after release of one hour's total bilateral renal arterial occlusion (P less than 0.001), but rose to normal within 24 hr. Poisoning with 4.7 mg/kg of body wt of mercuric chloride produced a cortical blood flow value that was 30% higher than control 24 hr after injection (P less than 0.01), while a 12 mg/kg of body wt dose gave a normal flow value. Inulin clearance was severely depressed in all models at all study times. Thus, in contrast to human acute renal failure, marked renal cortical ischemia is not an essential feature of these different forms of murine acute renal failure.

Acute Kidney Injury↗
PubMed1976

Acute renal failure caused by nephrotoxins.

Renal micropuncture studies have greatly changed our views on the pathophysiology of acute renal failure caused by nephrotoxins. Formerly, this type of renal insufficiency was attributed to a direct effect of the nephrotoxins on tubule epithelial permeability. According to that theory, glomerular filtration was not greatly diminished, the filtrate formed being absorbed almost quantitatively and nonselectively across damaged tubule epithelium. Studies in a wide variety of rat models have now shown glomerular filtration to be reduced to a level which will inevitably cause renal failure in and of itself. Passive backflow of filtrate across tubular epithelium is either of minor degree or nonexistent even in models where frank tubular necrosis has occurred. This failure of filtration cannot be attributed to tubular obstruction since proximal tubule pressure is distinctly subnormal in most models studied. Instead, filtration failure appears best attributed to intrarenal hemodynamic alterations. While certain facts tend to incriminate the renin-angiotensin system as the cause of the hemodynamic aberrations, others argue to the contrary. The issue is underactive investigation.

Acute Kidney Injury↗
PubMed1975

Role of prostaglandins in the pathogenesis of acute renal failure.

It is suggested that impaired glomerular infiltration in acute renal failure may be due, if only in part, to the derangement of a normal local feedback mechanism involving prostaglandins. According to this hypothesis, prostaglandins made in the medulla normally enter the loop of Henle and thus are present in distal tubule fluid reaching the macula densa. In the absence of direct vascular channels connecting the renal medulla with the outer cortex, this may be the only route by which medullary prostaglandins can reach the cortex without being destroyed by dehydrogenases. Under most circumstances in which renal perfusion and glomerular filtration fall, flow through Henle's loop continues, albeit at a reduced rate. This slowed flow through the loop and augmented prostaglandin release combine to produce a high concentration of prostaglandin in fluid leaving the medulla which, acting on the macula densa, counteracts the vasoconstrictor stimulus. If, however, filtration stops completely because of overwhelming vasoconstriction, flow along the loop also stops ans prostaglandins no longer reach the macula densa. Thus, the prostaglandin feedback loop would be opened, constrictor mechanism remain unchecked, and filtration failure perpetuated. It is proposed that such a self-perpetuating mechanism might operate in acute renal failure.

Acute Kidney Injury↗
PubMed1975

Active and passive immunization to angiotensin in experimental acute renal failure.

A number of studies support, and others fail to support, the concept that the renin-angiotensin system plays a key role in the pathogenesis of acute renal failure. This study, employing active and passive immunization against angiotensin II, was designed to examine the primacy of circulating angiotensin as a mediator of this syndrome. Neither mode of immunization significantly affected the degree of azotemia or the marked reduction of inulin clearance expected in rats subjected to glycerol-induced myohemoglobinuria. Twenty-four hours after challenge, inulin clearance (Cin) in actively immunized rats fell to 3.2% of control and that of unimmunized rats given the same dose of glycerol was 2.5% of control. Although there was some variation among groups of passively immunized rats, Cin of one group being 18% of control, Cin of the other groups was less than 3% of control. The dose and binding capacity of the immune globulin used here were essentially the same as those reported in another study in which immunization was thought to be of prophylactic value in rats subjected to s.c. administered glycerol injections. Technologic differences unrelated to immunization are suggested to have caused the difference in results in the two studies, and it seems doubtful that circulating angiotensin plays a key role in the pathogenesis of myohemoglobinuric acute renal failure in the rat.

Acute Kidney Injury↗
PubMed1975

Resistance to acute renal failure afforded by prior renal failure: examination of the role of renal renin content.

In this study, rats recovering from glycerol-induced acute renal failure were found to be protected from mercury-induced nephropathy, and HgCl2 poisoning protected rats from developing myohemoglobinuric renal failure. In view of the widely disparate nature of the renal failure models used, refractoriness appears to relate to an altered sensitivity of the organism itself rather than reflecting resistance to a particular nephropathic challenge. Renal renin content of the rats at the time of rechallenge was normal or high, a finding which contrasts sharply with that of chronically saline-loaded animals which also are refractory to ARF but have a maximally suppressed renal renin content. Renal renin depletion is not essential to the prevention of acute renal failure in the rat.

Acute Kidney Injury↗