Renal physiology最新文献

Renal functional adaptation to additional nephrons was studied in rats in which a third kidney was transplanted isogeneically. Total renal function did not increase when an extra kidney was added. Quantitation of the contribution of each kidney, by means of a 99mTc-DTPA scan, showed that the glomerular filtration rate of the native kidneys had decreased to counterbalance the added function. The glomerular filtration rate of the transplanted kidneys as well as its number of glomeruli were 20% less than that of the intact native kidneys. The present findings once again illustrate the kidney's remarkable capacity for functional adaptation to a change in the total number of nephrons.

Glomerular ultrafiltration of the plasma is a fundamental component of vertebrate renal function. The importance of the glomerulus is reflected by its near-universal presence and great elaboration among the vertebrates. Although the general structural features and functional properties of the glomerulus appear to be largely similar among diverse groups, there exists considerable variation in the magnitude of the rate of filtration. The kidney is the primary vertebrate organ responsible for water and metabolic waste excretion, and glomerular filtration plays an important role in these functions. Therefore, the magnitude of the GFR appears to be influenced primarily by the rates of water influx and metabolism. Major phylogenetic differences in morphological, physiological and metabolic design have a decisive impact on the magnitude of the GFR. The endothermic classes, with more numerous glomeruli, high metabolic rates, and high ultrafiltration pressures, have proportionately higher rates of glomerular filtration than the ectothermic groups. As a group, the reptiles, with presumably the lowest rates of water influx, exhibit the lowest GFRs. Within each class, there are trends toward species with greater access to free water having higher GFRs (e.g. fresh water vs. marine; mesic vs. xeric. The clearest examples exist for the teleosts, with marine forms having lower GFRs than their fresh water relatives. The coupling of the GFR to environmental influences is also demonstrated by the response of the animal to environmentally imposed perturbations, such as dehydration. In terrestrial animals during dehydration, reductions in the rate of glomerular filtration occur reducing the rate of urinary water loss. And increases in GFR appears to be important in the rapid elimination of water loads in nonmammalian vertebrates. This short-term modulation of the GFR occurs by either changing glomerular plasma flow or glomerular capillary hydrostatic pressure, or both. In addition, shifts in the filtering populations of glomeruli can take place, as has been demonstrated in birds. Although the mediators of these effects have not been unequivocally identified, several hormones, including antidiuretic hormone, angiotensin, and catecholamines, have been implicated.

The effect of lithium on p-aminohippurate (PAH) transport was studied using slices and basolateral membrane vesicles prepared from rat kidney cortex. The addition of lithium in concentrations ranging from 0.5 to 5 mM caused a concentration-dependent inhibition of PAH accumulation in the slices. Lithium inhibited PAH accumulation in the slices, not only during the rapid uptake period (after 10 min) but also during the approach to equilibrium (after 30 min). The effect of lithium (2 mM) in the slices was irreversible. The inhibitory effect of lithium was not the result of changes in the water distribution and the concentrations of ATP, sodium and potassium in the slices during incubation. The effect of lithium on the kinetic parameters for PAH accumulation was to decrease Vmax, while apparent Km remained constant. There was no lithium effect on the efflux of PAH from the slices back into the incubation medium, indicating that lithium inhibited PAH influx to the kidney cell. No evidence was obtained to indicate that lithium (1 mM) directly affected PAH uptake by isolated basolateral membrane vesicles. These results suggest that lithium seems to affect metabolism linked to the carriers for PAH transport other than ATP production and sodium gradient and then seems to decrease the mobility of the carriers in the membranes.

The physiological excretion of urinary protein is subject to great variation influenced not only by environmental and hormonal factors but also by genetics. The present study demonstrates that there is not only variation in respect to the excretion of plasma proteins but also of other types of proteins which are specific urinary proteins. There is a close relation between body weight and total protein excretion. However, male rats and mice do not fit the allometric line calculated for the other species studied. This is of special importance since these two species are often used in kidney research. The reason for this divergence in total protein is the excretion of sex-dependent low molecular weight proteins. The excretion of albumin, which is a marker of glomerular permeability and tubular reabsorption as well, shows a marked genetic variation between different rat strains. The data presented in this study demonstrate the general admissibility of transferring data from one species to the other but also the limitations in respect especially to the sex-dependent proteins which are excreted by some species.

The histochemical activities of nonspecific acid and alkaline phosphatases, NADH- and NADPH-tetrazolium reductases, alpha-glycerophosphate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were investigated in kidneys from rats treated with lithium and lithium plus neuroleptics. During the first 8 weeks of lithium treatment the activity of NADH-tetrazolium reductase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activity in the collecting ducts increased. The other enzymes did not change. After 8 weeks of treatment no further changes in enzyme activity occurred. Withdrawal of lithium caused normalization of enzyme activity after 8 weeks. A decrease in concentration ability was found in parallel with the increase in enzyme activities (p less than 0.001). The changes in enzyme activity were not significantly correlated to morphological changes in the collecting ducts. Treatment with neuroleptics alone caused no change in enzyme activity. During combined lithium plus neuroleptic treatment the enzyme activities changed in a similar way as during lithium therapy, but the changes were less pronounced. In parallel, a less pronounced decrease in concentration ability was found during this treatment.

The functional role of H1 and H2 receptors in mediating the effects of histamine on renal hemodynamics and tubular function was investigated in anesthetized dogs. Histamine, infused directly into the renal artery, caused decreases in renal vascular resistance and increases in total renal blood flow without significant changes in mean arterial blood pressure or glomerular filtration rate. These hemodynamic effects of histamine were inhibited by the H2-receptor antagonist, cimetidine, but not by the H1-receptor antagonist, tripelennamine. Histamine also caused increases in fractional urine flow and the fractional excretion of sodium and calcium with a concomitant decrease in urine/plasma osmolality. These tubular effects of histamine were antagonized by both tripelennamine and cimetidine. Histamine-induced increases in the fractional excretion of potassium were blocked only by tripelennamine. These results suggest that (1) both H1 and H2 receptors mediate the effects of histamine on urinary dilution and tubular reabsorption; (2) H2 receptors mediate the effects of histamine on renal hemodynamics, indicating that H2 receptors are present in the renal vasculature, and (3) H1 receptors may exist in the renal tubules.

A decrease of glomerular filtration rate can be observed during accelerated catabolism of ATP in kidney. It has been proposed that this effect is due to the increase in the renal production of adenosine from ATP. The last reaction in the pathway concerned is the conversion of 5'-AMP to adenosine. We found that brush border membranes purified from homogenates of the rat renal cortex carry out this reaction. The enzyme involved in the hydrolysis has the characteristic properties of ecto-5'-nucleotidases: It is inhibited by ATP, ADP, and by alpha, beta-methyleneadenosine-5'-diphosphate, and it is not stimulated by magnesium. All catalytic sites are accessible from the outside of the vesicles. The Km of the enzyme for 5'-AMP is 5.77 microM. The enrichment of the 5'-AMP-hydrolyzing activity in the brush border fraction as compared to the homogenate is 9.2 +/- 1.5 times. Histochemical staining of kidney sections reveals hydrolysis of 5'-AMP only at the brush border of the proximal tubule. We conclude that the brush border of the proximal tubule of the rat kidney possesses an ecto-5'-nucleotidase which has the same properties as the ecto-5'-nucleotidases in other tissues.

To examine the PGE2 and renin release during autoregulatory dilation of preglomerular vessels, experiments were performed in three groups of anesthetized dogs. By reducing the arterial perfusion pressure from 113 +/- 3 to 78 +/- 3 mm Hg, renin release rose to 20 +/- 50% and PGE2 release to 74 +/- 12% of the maximal values attained at two perfusion pressures below the range of autoregulation. During ureteral occlusion, PGE2 and renin release rose to maximal values already at control blood pressure and remained unaltered as the arterial perfusion pressure was reduced from 124 +/- 7 to 68 +/- 2 mm Hg. Renal blood flow fell in proportion to the perfusion pressure indicating abolished autoregulation. At a perfusion pressure below the range of autoregulation, saline infusion restored sodium excretion and reduced renin release but did not alter PGE2 release. We conclude that PGE2 release is raised by autoregulatory dilation of preglomerular arteries. Prostaglandins enhance renin release when afferent arterioles are dilated. Renin release mediated by a macula densa mechanism is not PGE2 dependent.

A study was made on the number of glomeruli in the outer cortex, midcortex, and inner cortex 4 weeks after 45 min of warm ischemia, using alcian blue to stain functioning glomeruli. During this time the stainable glomeruli in the kidney as a whole had decreased in number from 32,000 to 16,800. The superficial glomeruli were reduced by only about 30%, whereas in the juxtamedullary zones the number of functioning nephrons were reduced by 80%. This shows that the juxtamedullary nephrons are the most susceptible to degeneration in the recovery phase of acute renal failure caused by ischemia. The decrease in the number of glomeruli was accompanied by a reduction in total glomerular filtration rate to about the same extent. In contrast, the kidney weight was reduced by only about 20%, suggesting compensatory hypertrophy of the remaining tubules. Fluid reabsorption, urine osmolality, and potassium-secreting ability also remained decreased. The contralateral kidney responded with a compensatory hypertrophy and an increase in glomerular filtration rate, whereas the number of glomeruli in the cortex as a whole and in the individual cortical zones in this kidney remained the same as in control kidneys. It is suggested that the trapping of red cells in the juxtamedullary circulation seen soon after restoration of circulation to kidneys subjected to warm ischemia will also cause a further degeneration of the juxtamedullary nephrons.

The response of plasma renin activity (PRA) to stepwise reductions in renal arterial pressure (RAP) induced by suprarenal aortic constriction (SAC) or hydralazine (0.1-30 mg/kg i.v.), and the effect of indomethacin (5 mg/kg i.v.) or propranolol (1.5 mg/kg) s.c.) on the PRA response were examined in anesthetized rats whose right kidneys had been removed 6-7 days earlier. The stepwise reduction of RAP by SAC or hydralazine produced a steep increase in PRA when RAP was below approximately 100 mm Hg. Above this level, PRA was unaffected by changes in RAP. The SAC-induced increase in PRA was nearly abolished by indomethacin. On the other hand, propranolol failed to affect the SAC-induced increase in PRA. The hydralazine-induced renin release was remarkably suppressed by either indomethacin Or propranolol. These results suggest that SAC-induced renin release is mainly dependent on the prostaglandin system, whereas hydralazine-induced renin release is dependent on the prostaglandin and the adrenergic nervous system. We estimated the threshold pressure for increasing renin release is approximately 100 mm Hg.