Renal physiology最新文献

At present the detailed mechanism for transmembrane interactions is not known and a protein linked to the endoskeleton as well as to the exoskeleton has not been described as yet. The H2 complex, a transmembrane protein, consists of heavy and light chains, the latter is named beta-2-microglobulin. In order to look for an association of beta-2-microglobulin with an exoskeleton protein, we examined the extracellular matrix proteins, collagen type I, type IV, fibronectin, amyloid P, the solubilized glomerular basement membrane and laminin in respect to their interaction with the light chain. The heavy chain is known to bind strongly to the endoskeleton protein actin. Only laminin and the glomerular basement membrane bound firmly to the beta-2-microglobulin; 3 M urea was necessary to dissociate the formed complex. Incubation with beta-2-microglobulin antibody prevented binding of beta-2-microglobulin to laminin and the glomerular basement membrane on affinity chromatography columns. Antiserum to the glomerular basement membrane in turn prevented binding of beta-2-microglobulin to the glomerular basement membrane, whereas antibodies against the basement membrane collagen type IV failed to inhibit this binding to the glomerular basement membrane. Beta-2-microglobulin also bound to fibronectin but this complex was dissociated with 1 M urea. In a rosette assay beta-2-microglobulin antibody and antiserum to the glomerular basement membrane reduced attachment of glomerular cells to beads coupled with laminin and solubilized glomerular cells to beads coupled with laminin and solubilized glomerular basement membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Subcellular distribution of cathepsin B following subfractionation of the kidney cortex mitochondrial/lysosomal fraction by rate sedimentation indicates that this enzyme is mainly associated with the large, fast sedimenting lysosomes (protein droplets). A small proportion of cathepsin B is also present in the small lysosomes which cosediment with mitochondria, peroxisomes, and brush border and other large membrane vesicles. Amongst this broad spectrum of small lysosomes the distribution of cathepsin B, together with other acid hydrolases is associated with the more rapidly sedimenting lysosomes whilst cathepsin D differs in being associated with the slowest sedimenting lysosomes. Equilibrium banding in sucrose gradients shows the large lysosomes band at a density of 1.235 g/ml and that the small lysosomes have two distinct populations at densities 1.20 and 1.235 g/ml. Cathepsin B (and also cathepsin D and acid ribonuclease) appears to be associated only with lysosomes of high density. The various other acid hydrolases assayed are found in all the lysosomal populations. Small and large lysosomes of high density are very rich in a number of proteinases and therefore most probably represent lysosomal populations involved in the catabolism of proteins taken up from the glomerular filtrate.

The present study was performed to determine to what extent pH influences protein reabsorption in renal proximal tubule cells. Rat surface proximal tubules were microinfused in vivo with 125I-labelled albumin in buffer solutions at different pHs. Tubular uptake was determined as the difference between microinfused and urinary trichloroacetic acid-precipitable radioactivity. In separate experiments the tubular uptake was followed by electron microscope autoradiography. The results showed that the uptake at pH 4.5 and 6.0 was about 15% higher as compared to uptake at pH 7.4. Furthermore, the electron microscope autoradiography demonstrated that albumin is taken up by endocytosis at acid pH as under normal conditions.

A high-molecular-weight renin (HMWR) was detected in the plasma (molecular weight 50,600) and renal cortical homogenate (molecular weight 57,000) of 25-week-old male stroke-prone spontaneously hypertensive rats (SHRSP), in contrast to the renin with a molecular weight of 38,000 in normotensive Wistar Kyoto rats (WKY) and 5-week-old SHRSP. However, renin granules contained only the renin with a molecular weight of 38,000, indicating that the renal HMWR is not a native form but is probably a renin/renin-binding protein complex. Such HMWR was not produced when the renal cortex was homogenized with an equal amount of renal cortex of WKY. Further, the HMWR of the aged SHRSP was converted into the 38,000-dalton renin, when incubated with the extract of renal cortex of WKY. Thus, the existence of a renal cortical substance that converts the renal HMWR into the 38,000-dalton renin was evidenced. This substance was fractionated with DEAE-cellulose and was characterized as a putative SH enzyme. We conclude that a deficiency in the HMWR-converting substance may be attributed to the unusual formation of HMWR in the aged SHRSP.

A dynamic rat renal medullary model was employed to study how independent control of excretion of various substances is achieved. Salt and water reabsorptive coupling was heterogeneous in the distal nephron. Diversion of filtrate to juxtamedullary nephrons retained salt with little effect on water or urea, a response enhanced by concomitant reduction in inner medullary blood flow. Urine concentration required high permeability and low flow in medullary blood vessels and active inner medullary salt transport. Collecting duct urea movement was closely coupled to that of water and urea recycling was enhanced by incorporation of nephrovascular bundles.

The present light (LM) and transmission electron microscopic (TEM) studies were carried out to further document the anatomy of the 'superficial' juxtamedullary nephrons (SJMNs) located on the inside cortical surface of the rat kidney. TEM revealed that SJMNs possess all vascular and tubular cell types constituting the juxtaglomerular apparatus (JGA) in typical cortical and juxtamedullary nephrons (JMNs). Proximal to the glomeruli, epithelioid cells filled with secretory granules predominated in the media of afferent arterioles. The presence of renin in the granules was immunocytochemically demonstrated by the protein A-gold method. Further upstream from the glomeruli, epithelioid cells alternated with plain smooth muscle cells. The use of renin and angiotensin II antisera revealed similar arteriolar distributions of renin and angiotensin II positive cells in SJMNs as well as in typical JMNs. Numerous nerve terminals were found along afferent and efferent arterioles, suggesting a dense innervation of these vessels. The distribution of renin-containing (i.e., epithelioid) cells in the preglomerular arterioles was assessed in various nephron populations by LM using the PAP method and renin antiserum. In SJMNs, most renin-positive cells were found in the vicinity of the JGA along a mean arteriolar length of 35 +/- 3 micron (range 7-107 micron). In JMNs, renin-positive cells had a similar distribution along a mean arteriolar length of 35 +/- 1 micron. Scattered renin-positive cells were observed up to a maximal arteriolar length of 173 and 238 micron in SJMNs and JMNs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoregulatory efficiency of renal blood flow (RBF) and glomerular filtration rate (GFR) was evaluated in 12 anesthetized dogs that had been maintained on low-sodium diet during control conditions and following infusion of an angiotensin-converting enzyme inhibitor (captopril). Converting enzyme inhibition (CEI) decreased systemic blood pressure by 15.5 +/- 3.5%, increased RBF by 36.3 +/- 6.5%, and increased GFR by 25.9 +/- 10.7%. In response to reductions in renal arterial pressure, RBF was efficiently autoregulated and did not change significantly until the 89- to 75-mm Hg range during the control period and the 74- to 54-mm Hg range during CEI. Overall GFR autoregulatory efficiency was generally well maintained during CEI; however, evaluation of the coupled autoregulatory efficiency of RBF and GFR indicated that during angiotensin blockade, there was a greater incidence of a dissociation between RBF and GFR autoregulatory efficiency. Six of the 12 dogs showed reduced GFR autoregulatory efficiency at renal arterial pressures where RBF was still well maintained. Thus, while the data indicate that blockade of the renin-angiotensin system does not abolish the basic capability of the kidney to autoregulate either RBF or GFR efficiently, more subtle influences on the coupling of RBF and GFR autoregulatory efficiency were observed at the lower level of the autoregulatory range.

The alteration of renin-angiotensin-aldosterone system caused by diabetes mellitus was studied in streptozotocin-diabetic rats. The plasma renin activity (PRA), and plasma levels of angiotensin II (A II) and aldosterone (PAC) were measured in diabetic and age-matched control rats in 1, 2, 4 and 8 weeks after the intravenous injection of streptozotocin (50 mg/kg body weight). Diabetic rats showed the marked hyperglycemia persistently throughout the experimental period. On 1st week PRA, A II and PAC were significantly increased, and A II and PAC were also significantly elevated on 2nd week in diabetic rats compared with control rats. However, on 4th and 8th weeks PRA, A II and PAC in diabetic rats were significantly lower than those of control rats. Hematocrit values in diabetic rats were elevated on 1st week, normalized on 2nd and 4th weeks and then decreased on 8th week. These results may suggest that the hyperglycemia causes a biphasic alteration of renin-angiotensin-aldosterone system, i.e., early stimulated state due to volume depletion and later suppressed state due to volume expansion.