Summary. Although studies on the clearance of cndogenoasly circulating amino acids had been pub]i.shed for .several mammalian and non-mamiiialian vertebrate species, few data were available for the rat. Since micropunchire studies ou the renal handling of amino acid.s are mo.st couveuiently performed on thi.s species, endogenoas clearance studies have now beeu undertakeu using automated, iou-exchange chromatographic techniques for amino acid analysis. Endogeuous plasma amino acid concentrations were remarkably similar to those in man but renal clearances of most amiuo acids were cousiderably smaller, indicating highly cfficicut rcabsorpti\'e mechanisms; the urinary excretion patterns, also, were very similar to those of uiau, although a striking exception wa.s observed in the case of taurine, wliich was cleared iu the rat at rates approachiua 408' of the glouicnilar filtration rate. It was concluded that the renal haudling of amino acids, with the exception of taurine, was very similar iu rat aud uiau. so that couclusions drawn from micropuncture experiments in rats would seem likely to hold also for man. INTRODUGTION.In recent years our knowledge of the processes involved in the reabsorption of amino acids by the kidne\-has been greatly advanced by the study of individual renal tubules using technic^ues of free-flow micropuneture (Wci.se, Eisenbach and Stolte, 1972), microinjection (Bergeron and Morel, 1969), microperfusion (Chan andHuang, 1973; Silbernagl and Dectjen, 1972;Young and Freedman, 1971) and microperfusion combined with peritubular capillary perfusion (Lingard, Rnmrich and Young, 1973a, b). As for most other micropunctux'e experiments, the rat was used in all these studies, although, unfortunately, few endogenous amino acid clearance data are available for this speciesf." Died tragically on February 20, 1974. 1 Webber (1967, however, has reported rates of amiuo acid cxcrcttou iu developing rats and approximate clearauce values cau be computed from his data. In addition. Goyer, Reynolds aud Elston (1969) have published souie preliminary' clearance values incidcutally in a study on the effect of cycloieucine aduuuistratiou ou auiiuo acid excretiou. J. LINCARD, B. TURNER, D. WILLIAMS AND J. A. YOUNGThe present study, therefore, was imdertaken to provide this missing information, since the availability of endogenons clearance data would be of great help in interpreting results obtained from micropuncture experiments on individual renal tubules. MATERIALS AND METHODS.Male albino rats weighing about .300 g were used. They were allowed free access to normal food and water up to the beginning of the experiment, and, .since plasma ainino acid concentrations may fall during starvation (Wu, 1954), all clearance studies were completed within 4 h of withdrawal of food. To minimize the risk of contamination of collected urine with hair, food particles and faeces, tbe animals were first washed, following which they were allowed to dry themselves for a few minutes. To ensure an adequate urine flow, the animals wer...
Summary An equation has has developed to describe reabsorption and concentration profiles of organic compounds, such as amino acids and glucose, in the proximal kidney tubule under free‐flow conditions. Reabsorption is described in terms of a constant volume flux (Jv), an active: transport function showing saturation kinetics (with parameters Jmax, the maximum transport rate, and Ki, the half‐saturation constant), a passive diffusion term obeying Fick's Law (with permeability coefficient. P) and a solvent drag term (depending on the volume flux, Jv and the reflection coefficient δ). It was assumed, in general, that active transport and volume flux were related to tubule length rather than surface area and that transport rates were the same in the pars recta as in the pars concoluta. In the analysis, particular attention was paid to an assessment of the contribution of passive diffusion to the net transport rate off organic substances. It was found that, under normal conditions, the transport rates of most amino acids are set sufficiently high relative to the rate of water reabsorption that the value of the permeability coefficient can be charmed over a range of more than two orders of magnitude without causing substantial changes in the extent of net reabsorption attained by the end of the proximal convolution. Passive movement appears to play a very important role in stabilizing the value of net reabsorption since its effect balances that of active transport. In contrast, in cases where active transport rates are low, net reabsorption is determined largely by the magnitude of water Hux relative to the solute permeability so that the absolute permeability values become critical in determining the extent of reabsorption of a given solute. The effect of changes in plasma amino acid concentration on net reabsorption also varies according to the rate of active transport. If the plasma concentration is very low relative to the half‐saturation constant of the active transport mechanism, then net reabsorption remains relatively independent of plasma concentration and no saturation is observed. However, when this is not the case, net reabsorption becomes very sensitive to changes in plasma concentration.
Summary.Since the few data available concerning the effect of acid/base disturbances on renal amino acid reabsorption were conflicting, and there were sound theoretical reasons for an effect, we have studied the clearance of endogenous amino acids in the rat in vivo under control conditions and after induction of either metabolic acidosis or alkalosis by administration of NH4CI or NaHCO3, respectively. The effectiveness of treatment was assessed by examination of plasma and urinary levels of HCO3, Cl, Na and K. It was found that the renal clearance of amino acids, measured during acidosis or alkalosis, did not differ from those found under control conditions, the majority of values being less than t% of the glomerular filtration rate. Thus, the amino acid reabsorptive mechanism appears unaffected by changes in the pH of the glomerular filtrate and/or by changes in tubular hydrogen ion secretion which would accompany such disturbances. These data are thus in agreement with findings during acidosis in man and in both acidosis and alkalosis in the dog. The findings are contrary to earlier reports from in vitro studies in the rat, and suggest the presence of severe functional impairment in the isolated perfused kidneys used in these earlier studies where very large changes in amino acid clearance were obtained.
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