摘要:

We have recently reported that a lipid-lowering agent, probucol, reduces proteinuria in puromycin aminonucleoside (PA)-induced nephrotic rats (PAN). In this study, we examined whether a long-term treatment of hyperlipidemia with probucol can suppress the development of focal and segmental glomerulosclerosis (FSGS) in chronic PAN. A chronic PAN model was made with repeated intraperitoneal injections of PA (initially 100 mg/kg body weight followed by 25 mg/kg 5 times at 2-week intervals). Two weeks after the first injection of PA, either normal rat chow with or without 1% probucol was given to the nephrotic rats for 10 weeks. Chronic PAN exhibited remarkable proteinuria, hypoalbuminemia and severe hyperlipidemia with all lipoprotein fractions increased. Probucol treatment significantly reduced the lipid concentration in all major lipoproteins, significantly reduced proteinuria and increased plasma albumin concentration. Plasma albumin inversely correlated with cholesterol or phospholipid in low-density and high-density lipoproteins, suggesting that the lipid-lowering effect of probucol may ameliorate the hypoalbuminemia associated with nephrosis. In light microscopic examination, various degrees of FSGS with tubuloin-terstitial lesions were observed in the renal cortex from chronic PAN. The degree of FSGS was scored from grades 1 to 4 according to severity. One half of the untreated PAN (4/8) was classified into grade 4 and the other into grades 2 or 3, whilst one half of treated PAN (4/8) was classified either into grade 1 or 2. The grading of FSGS correlated negatively with plasma albumin concentration. These results demonstrate that probucol is highly effective upon nephrotic hyperlipidemia and suggest that a long-term treatment of secondary hyperlipidemia can suppress progressive renal injury associated with chronic nephrosis.

ISSN:1660-8151    

DOI:10.1159/000186806

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

To investigate the differences in the Na-K transport of the mesangial cell (MC) membrane in hypertension versus normotension, the activity of the Na-K pump and the passive cation permeability were measured in serially passaged cultured MC obtained from both spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. When Na-K pump was active, Na-K pump activity, described as ouabain-sensitive 86Rb uptake, was significantly greater in the cultured MC from SHR than WKY rats. The outward Na-K cotransport, described as the washout rate constant of bumetanide-sensitive 86Rb washout, was also greater in SHR MC than in WKY rat MC. When Na-K pump was inhibited by 1 mM ouabain, overall intracellular Na uptake was significantly greater in SHR MC. A greater 5-(N, N-hexamethylene)amiloride-sensitive Na uptake in SHR MC accounted for this difference. There was no difference in the intracellular concentration of Na and K in the cultured MC from the 2 strains when Na-K pump was active. It is concluded that there is an increased activity of Na-K pump in the cultured MC from SHR, and that this abnormality may be innate to SHR cells. It is also suggested that an increase in Na-K cotransport and Na-H antiport may explain this difference, and that these abnormalities observed in the SHR kidney may be involved in the pathogenesis of hypertension in this model.

ISSN:1660-8151    

DOI:10.1159/000186807

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In earlier studies, we have shown that induction of passive Heymann nephritis (PHN) by intrarenal infusion of anti-Fx1 A antibodies provokes an immediate fall in renal blood flow (RBF) and glomerular filtration rate (GFR). This was probably mediated via the complement system, as infusion of the F(ab’)2 fraction of anti-Fx1A did not reduce RBF and GFR. In the present study, the effects of α-adrenergic blockade upon the acute hemodynamic changes during induction of PHN and of C5a infusion were studied. Group 1 was infused with anti-Fx1A antibodies during blockade of the sympathetic nervous system with the α-blocker phentolamine; control animals were treated similarly, but infused with normal rat IgG. Group 2 was infused with the anaphylatoxin C5a, normally produced during complement activation, and compared with control animals infused with saline. In group 1, RBF did not differ from control animals after the infusion of anti-Fx1A antibodies (6.6 ± 0.5 compared to 7.3 ± 1.0 ml/min/g in the controls). GFR in the left, antibody-infused kidney fell compared to controls, and was 0.25 ± 0.08 ml/min/g at the end of the experiment compared to 0.60 ± 0.13 ml/min/g (p < 0.05 with Student’s t test, p = 0.07 with two-way analysis of variance (ANOVA). GFR in the right kidney remained unchanged compared to controls. In group 2, C5a induced a significant fall in RBF (from 7.9 ± 0.9 to 3.1 ± 0.4 ml/min/g kidney weight), significantly different from control animals where it fell from 8.1 ± 0.5 to 6.8 ± 0.7 ml/min/g (p < 0.0001 with two-way ANOVA, p < 0.001 with t test). GFR did not differ significantly from control animals. These results indicate that both the sympathetic nervous system and the anaphylatoxin C5a are mediators of acute hemodynamic c

ISSN:1660-8151    

DOI:10.1159/000186808

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

To evaluate the antihypertensive effect of magnesium lithospermate B isolated from Salviae miltiorrhizae radix, determinations of blood pressure and urinary excretions of sodium, potassium, prostaglandin E2 (PGE2) and kallikrein, which have been proposed to play an important role in the regulation of blood pressure, were made in rats with sodium-induced hypertension and renal failure. In rats given magnesium lithospermate B, blood pressure was significantly decreased, whereas urinary excretion of electrolytes was significantly increased. Urinary PGE2 excretion following administration of magnesium lithospermate B increased as the dose of the compound was stepped up. The activity of kallikrein in urine was also increased by the treatment. From these results, the blood pressure-lowering action of magnesium lithospermate B may be due in part to enhancement of the kallikrein-prostaglandin system.

ISSN:1660-8151    

DOI:10.1159/000186809

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The present study was undertaken to critically examine the hypothesis that circulating renotropin is the primary stimulus for compensatory renal growth. Blood was collected before and after either left nephrectomy or sham operation from a total of 34 rabbits and the serum renotropic activity assessed by the uptake of 3H-thymidine in primary cultures of rabbit kidney cells. Sera obtained after uninephrectomy had significantly more renotropic activity than sera collected before surgery. In some cases, sera obtained after sham operation had more renotropic activity than those collected before, but the mean response was not increased after sham operation. The difference between sera collected before and after uninephrectomy was not transferrable to primary cultures of rabbit liver cells. These data confirm a modest but significant influence of uninephrectomy on the renotropic activity of blood in rabbits.

ISSN:1660-8151    

DOI:10.1159/000186810

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Platelet-activating factor (PAF) is known as an important mediator in the pathogenesis of glomerular injury. In the present study, we evaluated the effect of the specific PAF antagonists CV-6209 and CV-3988 on accelerated nephrotoxic serum nephritis (NTN) in the rat. The amount of urinary protein excretion was significantly less in the rats treated with CV-6209 or CV-3988 on the 5th and 7th day of treatment than in the nontreated controls. The results of light- and immunofluorescence-microscopic examination did not demonstrate any favorable effect on glomerular changes by these PAF antagonists. However, CV-6209 protected against the loss of glomerular anionic charges in rats with NTN. Thus, it is suggested that PAF is a potent mediator of protein excretion, and that the loss of glomerular anionic charges is an important mechanism for the mediation of PAF in glomerulonephritis.

ISSN:1660-8151    

DOI:10.1159/000186811

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Hypertension is a well-known side effect of ciclosporin A (CsA). In the present study the mechanisms of vasoconstriction in renal vessels were examined in the isolated perfused rat kidney. Kidneys were perfused with constant flow at a temperature of 37 °C with Tyrode’s solution equilibrated with 95% O2/5% CO2. CsA was dissolved in ethanol. 500 and 2000 ng/ml increased resistance of renal vessels by 0.97 ± 0.55 × 105 and 2.29 ± 1.33 × 105 dyn s cm-5, respectively (mean values ± SD, n = 12). The vasoconstriction developed gradually over 4 min. The vasopressor effect of CsA was not changed by saralasin (10-6 M), nifedipine (10-6 M) and ketanserin (10-6 M), but was completely blocked by phentolamine and prazosin (each 10-6M). CsA-induced vasoconstriction was not prevented by perfusion with Ca2+-free solution containing 2 mmol EGTA. Similarly, pretreatment with reserpine to deplete sympathetic nerve endings from catecholamines did not affect CsA-induced vasoconstriction. The findings suggest that CsA-induced vasoconstriction is mediated by stimulation of α1-receptors. Ca2+ influx does not play a role for CsA-induced vasoconstriction. Prolonged perfusion of rat kidneys with the vehicle cremophor EL elicits an irreversible increase in perfusion

ISSN:1660-8151    

DOI:10.1159/000186812

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

A 60-year-old uremic patient treated with hemodialysis for 13 years developed acute hypotension during hemodialysis and overt heart failure subsequently in a period of relatively mild hypocalcemia after parathyroidectomy. Blood pressure during hemodialysis was maintained by continuous calcium infusion alone. Cardiomegaly was improved by normalization of serum calcium. The cardiac complication is considered to be exacerbation of the underlying myocardial dysfunction by the acute decline of serum calcium which might be a feature of the ‘hungry bone’ syndrome. Latent myocardial dysfunction might be exacerbated by only mild hypocalcemia after parathyroidectomy in long-term hemodialysis patie

ISSN:1660-8151    

DOI:10.1159/000186813

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1660-8151    

DOI:10.1159/000186814

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:1660-8151    

DOI:10.1159/000186815

出版商:S. Karger AG    

年代:1992

数据来源: Karger