Renal physiology最新文献

The phosphorylation of rat renal brush border membrane protein was analyzed after incubation of cortical slices with 32P-orthophosphate and compared with the phosphorylation by gamma-32P-ATP of isolated brush border vesicles. Phosphate incorporation into brush border membranes isolated from slices was linearly related to the incubation time as well as to the specific activity of orthophosphate present during slice incubation. Incorporation of phosphate into proteins reached an equilibrium after about 60 min, whereas incorporation of phosphate into lipids increased continuously. In brush border membranes isolated from slices incubated with orthophosphate (32P), the addition of cAMP or theophylline produced a dephosphorylation of a 47,000-dalton protein; no increased phosphorylation was observed. In brush border membranes, phosphorylated with gamma-32P-ATP, cAMP and dibutyryl cAMP (dB-cAMP) produced an increase in phosphorylation but no dephosphorylation. Sodium-dependent phosphate transport in brush border membranes was not altered by an incubation of slices with cAMP or dB-cAMP. These observations suggest that the phosphorylation machinery of isolated rat renal brush border membranes does not correspond with the mechanisms leading to phosphate incorporation into brush border membrane proteins in the intact cell.

The similarity (or lack of) of mechanisms for ion and water transport across segments of the distal nephron of the various vertebrate classes is considered. Except for the reptilian distal nephron, the early distal nephrons from vertebrates of different classes appear to share certain morphological and functional characteristics. Among these are a relative impermeability of the tubule to water and the ability to preferentially reabsorb solute. This osmodilution of the luminal contents seems to be attributed to the presence of a sodium-chloride cotransport system located in the lumen membrane. The characteristics of solute and water transport of the late distal tubule are also considered. The available data suggest that there are striking similarities for the solute transport characteristics of the various vertebrate classes which have been studied. On the other hand, not all vertebrates appear to have developed the hydroosmotic response to antidiuretic hormone that has been observed in the mammals.

Hormones influence renal function by both extrarenal and intrarenal mechanisms. Extrarenal mechanisms include the effects through systemic hemodynamic and neural pathways, whereas intrarenal mechanisms can be largely divided into the effects on intrarenal hemodynamics and those on tubular transport epithelia. Neurohypophysial hormones and the renin-angiotensin system appear to act primarily on systemic and preglomerular vasculature in primitive vertebrates, while direct tubular action appears to have evolved at a later stage of phylogeny. Although aldosterone is an essential hormone for fluid mineral balance in mammals, the action of mineralocorticoids on tubular Na transport has not been established in nonmammalian tetrapods. In bony fishes in hyperosmotic environments, cortisol accelerates active Na extrusion from the gill. In contrast, prolactin is important for maintaining low osmotic water permeability of the transport epithelia in fishes in hypoosmotic media. Thus, both function and site of hormone action appear to have changed during the evolution of vertebrates interacting with changing environments, and in response to the demands from other bodily functions. Furthermore, evolution of interactions, at the cellular level, between systemic and locally formed hormones such as prostaglandins, kinins, and perhaps angiotensin may have developed more elaborate controlling systems of renal handling of solutes and water.

The effect of verapamil, a Ca++ antagonist drug, on renal function and proximal fluid reabsorption in normal and hypertensive (GII) rats was studied. During intravenous infusion of verapamil, mean arterial pressure (MAP) fell significantly in both groups, 23% more in hypertensive than in normotensive rats. Glomerular filtration rate (GFR) was significantly higher in hypertensive rats and also increased significantly in this group during verapamil infusion. Effective renal plasma flow (ERPF) was similar in both groups and did not change significantly during verapamil infusion. The increase in urine flow, Na+ and Ca++ excretion was higher in hypertensive than in normotensive rats during verapamil infusion. When 10(-5) M verapamil was added to the luminal perfusate of proximal tubules, fluid reabsorption was reduced to 64% in normotensive and to 42% in hypertensive rats. When added to capillary perfusate, fluid reabsorption was almost completely but reversibly inhibited (92% in normotensive and 83% in hypertensive rats). Our findings indicate a direct effect of verapamil on renal Na+ and possibly also on Ca++ reabsorption, suggesting involvement of the Na+-Ca++ countertransport system. The greater effect of verapamil on Na+ excretion in hypertensive rats was not due to increased action on proximal Na+ reabsorption.

Renal catecholamine concentrations and urinary dopamine excretion from the isolated perfused kidney were measured in intact and peripherally sympathectomized rats. Urinary dopamine excretion was not diminished by sympathectomy, was increased by l-dopa (but not tyrosine or dopamine 4-O-sulphate) in the perfusate and was virtually abolished by prior treatment with the dopa decarboxylase inhibitor, carbidopa. These results confirm the importance of renal extraneuronal dopamine production, from circulating l-dopa, as a contributor to urinary dopamine excretion.

Autoradiography showed that 3H-labelled alcian blue injected into the rat renal artery was concentrated in the glomeruli. To test if the uptake could be used as a measure of local glomerular plasma flow, the one-pass extraction was measured in 19 rats. The average extraction was 31.9% (SD 8.0%). Impurities and heterogeneity of the tracer as well as reversible binding to erythrocytes may have contributed to the low estimated extraction. The average extraction of 103Ru-ruthenium red was 26.3%. We conclude that neither of these dyes are suitable for measurement of glomerular plasma flow.

Metabolism of very low density lipoprotein-triglyceride (VLDL-TG) was studied in the isolated perfused rat kidney (IPRK). Recirculating perfusate consisted of Krebs-Henseleit bicarbonate buffer containing 6% defatted albumin and VLDL-TG which has been labelled in vitro with 14C-tripalmitin. Results show that the IPRK catabolizes VLDL-TG. Renal removal of VLDL-TG from perfusate was impaired in the presence of 1.0 mM palmitate. A lower palmitate concentration, 0.4 mM, was without effect. It is concluded that high concentrations of circulating free fatty acids impair renal metabolism of fatty acids derived from VLDL-TG.

Considerable discrepancies exist in the literature concerning Na excretion by the rat kidney in experimental antiglomerular basement membrane (GBM) glomerulonephritis (GN). Previous studies in our laboratories demonstrated a disturbance in Na excretion with an impaired absolute (UNa X V) and fractional (FENa) excretion of Na after saline loading. However, most of the other authors in the literature failed to observe similar findings. The present study was undertaken to elucidate some of these controversies: We showed that a difference in Na excretion between anesthetized GN and normal rats might not be detected after a volume expansion if the latter is small or slow (FENa in GN 2 +/- 0.1%, in normals 2 +/- 0.2%; not significant). Only a rapid and important volume expansion is sufficient to unmask such a difference between the two groups (FENa 3 +/- 0.3 and 6 +/- 1%, respectively, p less than 0.001), and detect an impaired Na excretion in GN animals. The same amount of NaCl was nevertheless administered during slow and rapid volume expansion. Similarly, in GN conscious rats only after a saline load or repeated water loads did we observe a significantly smaller UNa X V compared to normals while no difference was present between the two groups after a single water load. In the literature, all the authors, that failed to demonstrate a disturbance in Na excretion in anti-GBM GN, administered slow and small isotonic saline loads to their rats. The hypothesis we formulate to explain these controversies is that the nonobserved disturbance in sodium excretion in most of these studies is probably secondary to insufficient natriuretic stimuli.