In experiments designed to analyze cardiovascular structure in response to antihypertensive therapy with an ACE inhibitor, we decided to start very early in life with the aim to prevent blood pressure increases and the development of vascular structural changes. In these treated groups of rats we unexpectedly observed that after they were weaned, their water consumption and urine volume, respectively, increased substantially. The present study was designed to determine if inhibition of the renin-angiotensin system produced similar effects in different strains of rats, and focused on characterizing the abnormal fluid balance occurring as a consequence to neonatal treatment with ACE inhibitors or angiotensin II blockers. Three-day-old Wistar Kyoto (WKY), Wistar (WR) and spontaneously hypertensive rats (SHR) were given either saline, enalapril, captopril, losartan and the AT2 blocker, PD123319, in the same amount of volume for 20 days. Treatment was stopped and rats were examined with regard to renal morphology at 4, 14 and 30 weeks of age. In addition, water consumption, urine volume, urine electrolytes and osmolality were analyzed at 14 weeks of age, that is, 10 weeks off treatment. Early treatment with the ACE inhibitors, enalapril and captopril, and the AT1 blocker, losartan, but not the AT2 blocker, PD 123319, in the SHR and in the normotensive strains WKY and WR produced persistent, irreversible histopathological renal abnormalities in adult life, long after the rats had been taken off treatment. These abnormalities consisted of mainly cortical tubulointerstitial inflammation, various degrees of papillary atrophy and pelvic dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced glomerular filtration rate (GFR), not due to hypovolemia, has been reported in patients in the proteinuric phase of the minimal change nephrotic syndrome (MCNS). A group of children with MCNS was studied to investigate the possible relationship between the fusion of glomerular epithelial foot processes and the reduction in GFR. The degree of foot process fusion was estimated as the harmonic true mean of foot process width and the length density of epithelial slit pores as determined by quantitative electron microscopic stereology. In the patients investigated GFR ranged between 40 and 127 ml/min/1.73 m2 body surface area, the filtration fraction between 6.9 and 22.5%, and the serum albumin concentration between 14 and 46 g/liter. The mean foot process width, which varied between 330 and 870 nm, showed a close correlation with GFR (r = -0.859) and the filtration fraction (r = -0.812), as well as with the serum albumin concentration (r = -0.756). As expected, a reduction of epithelial slit pore length occurred concomitant with the broadening of the foot processes. These results agree with the hypothesis that the reduction in the total length of glomerular epithelial slit pores, due to the fusion of foot processes, results in a reduced glomerular capillary permeability to water and small solutes.

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ANGG~RD, E., S. 0. BOHMAN, J. E. GRIFFIN 111, C. LARSSON and A. B. MAUNS-BACH. Subcellular localization of the prostaglandin system in the rabbit renal papilla. Acta physiol. scand. 1972. 84. 231-246. The occurrence of prostaglandins (PG), prostaglandin precursor acids, prostaglandin synthetase and 15-hydroxy prostaglandin dehydrogenase was studied in subcellular fractions isolated from homogenates of rabbit renal papilla by sucrose density gradient centrifugation. The investigated fractions were lipid droplets, supernatant, microsomes and mitochondria as verified by electron microscopy. Most of the prostaglandins was found to be prostaglandin E2 and was present in the supernatant whereas the prostaglandin synthetase occurred most abundantly in the micro-soma1 fraction: Nearly all of the recovered prostaglandins were formed during the preparation of the subcellular fractions. Arachidonic acid was the major esterified Czo acid and had the highest relative concentrations in the supernatant, microsomes, and mitochondria, whereas the lipid droplets had lower concentrations. No detectable 15-hydroxy prostaglandin dehydrogenase was present in the supernatant fraction of the papilla. The results indicate that in the rabbit renal papilla prostaglandin E2 is formed mainly from locally available arachidonate in membranes which sediment in the microsomal fraction and which may be derived from either cell membranes or membranes of the endoplasmic reticulum. After their formation the prostaglandins are probably released into the cytoplasm of the cells rather than being concentrated within specific subcellular particles and may leave the papilla without undergoing metabolic inactivation.The original discovery that the renal medulla contains appreciable quantities of prostaglandin-like material (Lee et al. 1965) has since been extended in several directions. The major prostaglandin was identified as prostaglandin E2 (Daniels et al. 1967, Lee et al. 1967 or closely related compounds. The biosynthesis of PGEfrom 3H-labelled arachidonic acid was demonstrated in rabbit renal medulla by Hamberg (1969). PGEz was observed to be released in renal venous blood after ischemia (McGiff et al. 1970 a, Edwasds, Strong and fiunt 1969), nerve stimulation (Dunham and Zimmerman, 1970) angiotensin (McGiff et al. 1970 b) and into renaI lymph following injection of noradrenaline (Fujimoto and Lockett 1969). 23 1 232 E. X N G G h D ET AL.Since prostaglandin E-compounds antagonize the actions of antidiuretic hormone (Orloff, Handler and Bergstrom 1965, Orloff and Grantham 1966, Johnston, Herzog and Lauler 1967 and have strong natriuretic effects (Herzog, Johnston and Lauler 1966, Johnston et al. 1967 b) a physiological role has been suggested for PGE-as an intrarenal modulator of salt and water excretion.The interstitial cells of the renal medulla contain numerous lipid droplets and have been assigned secretory functions (Gloor and Xeiditsch-Halff 1965, Bulger and Trump 1966. Osvaldo and Latta 1966. Nissen 1967. The lipid droplets accumulate dur...

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SUMMARYKidney graft biopsies were performed 2-3 yr after transplantation in eight type I (insulin-dependent) diabetic patients who had previously been subjected to kidney transplantation (six patients) or combined kidney and segmental pancreas transplantation (two patients). In five of the six patients that had undergone only kidney transplantation, light microscopic examination of the graft biopsy revealed changes compatible with diabetic nephropathy, and electron microscopic morphometry showed a thickening of the glomerular basement membrane (GBM). In the two patients who had been subjected to combined pancreas and kidney transplantation, the kidney graft biopsy showed no light microscopic changes suggestive of diabetic nephropathy, and electron microscopy showed no thickening of the GBM. Thus, it appears to be possible to prevent the recurrence of diabetic nephropathy in human kidney allografts by simultaneous pancreas transplantation. DIABETES 1985; 34:306-308.

The aim of the present investigation was to measure the back-leak of pelvic urine to the blood circulation. In normopenic hydronephrotic, dehydrated hydronephrotic and dehydrated control kidneys the back-leak was estimated from a servocontrolled machine which regulated infused saline to keep a present pelvic pressure constant. The disappearance of fluid from the renal pelvis could be measured at different pressure levels, and a pressure-dependent outflow of fluid was found. From these measurements a back-leak conductance could be calculated which proved to be independent of pressure. In the lower pressure range (15-20 mmHg) there was a significantly lower conductance in the dehydrated controls compared with the dyhydrated hydronephrotic kidneys, while in the higher pressure range (25-30 mmHg) no difference was found. From electron microscopical studies the pyelorenal back-leak of fluid in both hydronephrotic and control animals seemed to be most pronounced in the fornix region, as documented by a heavy presence of horseradish peroxidase in the intracellular spaces there. Other experiments with radioactively labelled inulin, which was injected into the pelvic cavity, indicated that most of the back-leak occurred via the renal blood vessels and not through the lymphatic system. The importance of this back-leak was evident from the measurements of the total kidney glomerular filtration rate (GFR) at a slightly increased pelvic pressure, where some of the urine with radioactive tracer flows back to circulation. The back-leak of pelvic urine could also affect the concentration mechanism by removing diluted urine which had flowed over the renal papilla, and through water and urea diffusion increased papillary interstitial osmolarity.