摘要:

A number of chemical modifications in the spironolactone molecule were attempted over the last decade to synthesize ligands with high affinity for the mineralocorticoid receptor (MCR), and for possible use in the clinical control of the hypertensive disease. ZK 91587 has been commercialized as the ‘ideal’ ligand for the MCR, replacing the natural hormone aldosterone. None of the derivatives was retained for possible clinical use as an improvement over Canrenone or Spironolactone. No apparent correlation could be drawn between affinity for the MCR in vitro and biological potency in vivo. Such considerations challenge classical notions regarding the receptor mediated hormone act

ISSN:1420-4096    

DOI:10.1159/000173409

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The biological characteristics of a kidney growth factor (KGF) from uninephrectomized rat plasma have been studied. A crude preparation of this factor [Nephrol. Dial. Transplant. 4: 334–338,1989] was further purified by hydrophobic interaction HPLC and gel filtration. KGF was found to be a heat- and trypsin-resistant protein. This factor stimulated dose-depend-ently DNA synthesis by the mouse kidney in vivo, and by either rat renal tubules or serum-deprived LLC-PK1 cells, in vitro. KGF also increased protein synthesis in these cells, in a dose-dependent manner. Moreover, KGF stimulated sodium uptake by these cells, associated with the maximal increase of protein synthesis. Our findings indicate that KGF is a potent renotropic protein which can play a key role in the renal compensatory growth after uninephrectom

ISSN:1420-4096    

DOI:10.1159/000173410

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Tamm-Horsfall protein (THP), a normal constituent of mammalian urine, has been determined in rat urine under various conditions in an attempt to elucidate the physiological role of this glycoprotein. Experiments were designed to assess whether THP production is related to the process of urine concentration or to the transport activity of the thick ascending limb of the loop of Henle (TAL), the nephron segment where it is produced. For this purpose, THP excretion was measured, by radioimmunoassay, in adult male rats under 4 different conditions induced by the following chronic treatments: (1) furosemide (12 mg/day in osmotic minipumps); (2) increased water intake; (3) antidiuretic hormone (ADH) infusion (50 ng DDAVP/day in osmotic minipumps) in rats of the Brattleboro strain with hereditary hypothalamic diabetes insipidus; (4) high-protein (32% casein) versus low-protein diet (10% casein). Each experiment included 6 experimental and 6 control rats. After treatment for 1–3 weeks, 24-h urines were collected for determination of urine flow rate, osmolality, and creatinine and THP concentrations. No significant changes in THP excretion were observed in experiments (1) and (2) despite 5- to- 7 fold-differences in urine flow rate. Antidiuretic hormone treatment in (3) slightly lowered THP excretion (287 ± 53 vs. 367 ± 41µg/day per 100 g body weight; p < 0.005), whereas high-protein diet, in experiment (4), led to a 50% increase in THP excretion (446 ± 57 vs. 304 ± 79 µg/ day per 100 g body weight; p < 0.001). Expressing THP excretion relative to that of creatinine did not change these findings. These results show (1) that chronically established changes in the level of diuresis, chronic furosemide-induced blockade of the NaKCl-cotransporter or the absence of ADH in Brattleboro rats have little or no impact on the level of THP production, and (2) that THP production is independent of the intensity of transport in the TAL, since two conditions which both are known to increase the transport rate of solutes in the TAL (ADH infusion and high-protein diet), resulted in opposite changes in THP excretion. It is concluded that the rate of THP synthesis is neither linked to the process of urine concentration nor to the ion transport activity of

ISSN:1420-4096    

DOI:10.1159/000173411

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Rats with a high number of superficial nephrons (MWF/Ztm) also show an elevated urinary protein excretion and a high systolic blood pressure. To investigate a possible correlation between the number of superficial glomeruli and these physiological changes, MWF/Ztm rats were crossed and backcrossed to Wistar cryptorchic (WC/Ztm) animals with no superficial nephrons in order to produce genotypes with differing numbers of superficial glomeruli. In the parental strains, the F1 hybrids and the 8 possible backcrosses, the number of superficial glomeruli, the distance of the 10 most superficial glomeruli to the renal surface, and the diameter of Bowman’s capsules were determined by morphometric analysis. The excretion of total protein, in detail low molecular weight proteins, albumin, and high molecular weight proteins were measured quantitatively in 5 males of each genotype. Systolic blood pressure was determined by a tail-cuff method in conscious rats. Means of each variate of the 12 available genotypes were linearly correlated and demonstrate a close correlation between the amount of superficial nephrons and the observed physiological changes, i.e. the more superficial the glomeruli the higher the urinary protein excretion, especially albumin, and the higher the systolic blood pressur

ISSN:1420-4096    

DOI:10.1159/000173412

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Acute addition of adenosine triphosphate (ATP) stimulated thymidine incorporation in confluent, quiescent primary cultures of rabbit renal proximal tubule cells in a dose-responsive manner. Similar increases in thymidine incorporation was observed with adenosine diphosphate and adenosine monophosphate but not with adenosine. The effect of chronic administration of ATP, however, suppressed cell growth. This suppression appears to be due to an effect of ATP to cause detachment of cells from culture plates, resulting in an increase in thymidine incorporation acutely but in suppression of cell growth chronically. ATP is, therefore, not a direct growth promoter of renal proximal tubule cells in primary culture.

ISSN:1420-4096    

DOI:10.1159/000173413

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In a previous study, we tested the hypothesis that an elevated level of renal glutathione (GSH) would protect the kidney from ischemic injury. However, prior elevation of GSH with GSH monoethylester enhanced the injury induced by 35 min of ischemia and blood reflow [Scaduto RC Jr, Gattone VH, Grotyohann LW, et al; Effect of an altered glutathione content on renal ischemic injury. Am J Physiol 1988;255:F911-F921]. Additionally, GSH monoethylester produced morphologic alterations in the absence of ischemia. Thus the greater ischemic injury observed after GSH ester pretreatment could have been due to a synergistic effect between the events caused by ischemia and the pretreatment. The present study was conducted to evaluate the utility of elevating renal GSH levels by administration of GSH. Administration of GSH (1 mmol/kg body weight) caused a 3-fold elevation of renal GSH levels and a 6-fold elevation of renal cysteine levels after 60 min without causing changes in renal morphology or GFR. After 35 min of renal artery occlusion and 90 min of blood reflow, animals pretreated with GSH had a much greater decline in GFR than untreated control animals. This enhancement of renal ischemic injury in GSH-treated animals was similar to that observed following administration of GSH monoethylester. We conclude that administration of GSH is the method of choice for elevation of renal GSH and that elevation of renal GSH leads to an enhanced ischemia-induced injury which is independent of the method employed to elevate renal GSH.

ISSN:1420-4096    

DOI:10.1159/000173414

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173415

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173416

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173417

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1420-4096    

DOI:10.1159/000173408

出版商:S. Karger AG    

年代:1991

数据来源: Karger