摘要:

Because of the prominent role of the renal medulla in the elaboration of concentrated urine and the possible differential regulation of the various nephron segments, desensitization to vasopressin (AVP) was studied on freshly isolated rat medullary thick ascending limbs (MTALs) and outer medullary collecting ducts (MCDs). Desensitization was induced through intramuscular injections of 1-deamino-8-D-arginine-vasopressin (dDAVP, 2 µg/day for 3 days), the last of which was performed 1 h before kidney removal. The cellular response to AVP was studied by measuring cAMP accumulation in micro-dissected nephron segments. In the MTAL, we observed a marked (around 80%) and selective desensitization to AVP, the response to either glucagon or human calcitonin remaining unaltered. In the MCD significant desensitization was observed in the presence of 1 nM AVP in the assay medium, and was no longer significant when the AVP concentration was increased to supramaximal levels (10-1,000nM). These experiments thus reveal a clear dissociation between MTAL and MCD with regards to dDAVP-induced desensitization and extend previous observations made on target segments in the renal cortex

ISSN:1420-4096    

DOI:10.1159/000173442

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

It is known that intact prostaglandin synthesis is of some importance for tubuloglomerular feedback (TGF). In this study the effects of cyclooxygenase inhibition by oral fenflumizole, an imidazole derivative on TGF in rats after acute elevation of ureteral pressure were investigated by comparison with the TGF mechanism in untreated rats. The effects of fenflumizole on the TGF mechanism were also compared with those of indomethacin injection. To characterize the TGF mechanism proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with an artificial perfusion solution with a composition resembling that of the proximal fluid. The perfusion rate was varied from 0 to 40 nl·min-1, in steps of 2.5-5 nl·min-1, permitting measurement of the maximal pressure response ΔPsf, to increased tubular perfusion, and the perfusion rate which elicited a half-maximal drop in Psf, designated the turning point (TP). Both cyclooxygenase inhibitors caused a significant increase in TP from a control value of 21 to approximately 27 nl·min-1. TP remained at this level in fenflumizole-treated rats, even after elevation of ureteral pressure, a situation in which TGF is normally not detectable. From these and earlier investigations we conclude that the prostaglandin system is of importance for a normally operating TGF control mechanism, both under normal conditions and, especially, in conditions in which resetting of TGF is obser

ISSN:1420-4096    

DOI:10.1159/000173443

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Atrial natriuretic factor (ANF) has been shown to be effective in reversing renal functional impairments following renal ischemia. We studied the effects of a nonhypotensive intravenous ANF infusion (100ng/min × kg BW, 60 min) after 90 min unilateral renal arterial occlusion in anesthetized dogs with an intact contralateral kidney. ANF plasma levels remained unchanged in controls (group 1) and increased in ANF-infused animals (group 2) from 22 ± 3 to 552 ± 124 pg/ml. Blood pressure increased in both groups during renal ischemia, but returned to control values in group 2 when ANF infusion was started. Plasma vasopressin did not change in groupl, but increased in group 2 (0.77 ± 0.29 vs. 1.10 ± 0.49 pg/ml) after terminating ANF infusion. The postischemic fall in creatinine clearance (CCr) filtration fraction (FF) and renal blood flow (RBF) was prevented by infusion of ANF (Ccr: group 1, 0.16 ± 0.05 vs. group 2, 1.01 ± 0.25 ml/min × kg BW; FF: groupl, 4.0 ± 1.6 vs group2, 14.114.1%; RBF: groupl, 6.0 ± 1.2 vs. group 2,9.2 ± 1.6 ml/min × kg BW); however, the effects were limited to the time of infusion and the postischemic increase in urinary excretion of the proximal tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG; group 1, 317.7 ± 163.6 vs. group 2, 672.4 ± 245.7 µU/min × kg BW) was not improved by ANF Our data suggest that infusion of ANF transiently reverses postischemic renal impairment. However, the failure to demonstrate a sustained postischemic improvement of renal functional parameters and to ameliorate massive NAG excretion casts doubt on the benefit of ANF infusion in preventing

ISSN:1420-4096    

DOI:10.1159/000173444

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The renal handling of sodium and calcium in spontaneously hypertensive rats (SHR) was investigated over an extended period (10-75 weeks of age) and compared with age-matched normotensive Wistar-Kyoto controls. The animals were fed a standard rat chow except during screening periods when liquid diet that matched the pellet chow was substituted. Sodium balance, urinary excretion of sodium and calcium, fractional excretion of sodium (FENa), and renal cortical dopamine receptors (DA1 and DA2) were measured at 10, 30, 60 and 75 weeks of age. The results showed no difference between the two strains except for FENa, which was significantly higher in the SHR at 75 weeks coincident with decreased glomerular filtration rate. We conclude that a defect in renal handling of sodium and/or calcium is not a major factor in the maintenance of hypertension in the SHR.

ISSN:1420-4096    

DOI:10.1159/000173445

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

To investigate the permeability properties of the basement membrane beneath macula densa cells and between extraglomerular mesangial cells, thick ascending limbs with attached glomeruli were dissected from rabbit kidney and incubated in a Ringers solution containing either horseradish peroxidase (HRP) (1 mg/ml; molecular weight -40,000) or native or cationic ferritin (both at 5 mg/ml molecular weight -450,000) for 5 and 20 min at room temperature. Tubules were processed for electron microscopy. At both time points, HRP reaction product fully permeated the matrix material between extraglomerular mesangial cells, the basement membrane underneath the macula densa, and also was occasionally located in intercellular spaces and intracellular vesicles within macula densa cells. Similar results were obtained with native and cationic ferritin. In separate experiments, thick ascending limbs with attached glomeruli were perfused for 20 min at room temperature with a Ringer solution containing HRP (1 mg/ml). HRP was found in tubulovesicular bodies within the apical cytoplasm of macula densa cells again indicating that these cells exhibit endocytotic activity. However, HRP did not gain access to intercellular spaces indicating that the apical junctional complex was impermeable to HRP. These results demonstrate that the macula densa basement membrane and matrix material between extraglomerular mesangial cells is permeable to high molecular weight molecules and suggest unhindered diffusion of water and solutes within this area.

ISSN:1420-4096    

DOI:10.1159/000173446

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) observed after the administration of the carbonic anhydrase inhibitors acetazolamide and benzolamide had been explained as due to activation of the tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this pathway should prevent the development of renal vasoconstriction with the carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole kidney the effect of acetazolamide (20 mg/ kg body weight) in the presence or absence of furosemide (5 mg/kg body weight), a drug which blocks the tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF (18%). By contrast with the effects of acetazolamide, furosemide did not alter GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis without changes in urinary bicarbonate excretion. The infusion of acetazolamide in furosemide-treated dogs resulted in a significant increment in renal bicarbonate excretion and in a significant reduction in the levels of both GFR (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide-induced reduction in both GFR and RBF cannot ba accounted for by changes in chloride levels in the juxtaglomerular region due to enhanced salt transport in the macula densa/distal nephron. The increased renal vascular resistance observed with acetazolamide might occur by either a direct effect of this agent on the renal circulation or as a result of changes in intrarenal pressure secondary to the inhibition of proximal fluid reabsorption.

ISSN:1420-4096    

DOI:10.1159/000173447

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Rats were given a 4- to 6-mg/kg body weight intraperitoneal injection of the antitumor drug, Cisplatin, 5-7 days prior to experiments to study tubule acidification by clearance and stationary microperfusion techniques. Cisplatin reduced the glomerular filtration rate markedly and caused a moderate degree of metabolic acidosis, but urine acidification (pH) was well maintained. Proximal tubule stationary pH and bicarbonate concentrations, as measured by pH microelectrodes, were significantly increased. The defect of proximal H+ secretion is reflected by increased acidification half-times (from 4.44 to 10.2 s) and reduced bicarbonate reabsorption to 37% of control values. H-ion back flux, measured during tubule and capillary perfusions with Ringer’s bicarbonate- and CO2-free phosphate solutions, was reduced to 68% of control values. The apparent H-ion permeability was lowered from 0.79 to 0.54 cm/s. These results indicate that proximal acidification is reduced by impairment of H+ transport and not by increased transepithelial H+ shunting. Blunted acidification is compatible with a reduction in the number of Na/H exchangers in the proximal brush border and/or a decrease in the apical sodium gradient, the driving force for proximal H-ion secretion. Cortical distal tubule acidification, measured by double-barreled ion-exchange resin/PD microelectrodes, was not significantly affected by Cisplatin. This accounts for the observation that, in spite of the impaired proximal acidification, urine pH is kept within the normal rang

ISSN:1420-4096    

DOI:10.1159/000173448

出版商:S. Karger AG    

年代:1992

数据来源: Karger