Chronic Partial Ureteral Obstruction in the Neonatal Guinea Pig. II. Pressure Gradients Affecting Glomerular Filtration Rate

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Abstract
Neonatal guinea pigs with chronic partial ureteral obstruction (CPUO) and contralateral nephrectomy develop hydroureteronephrosis and reduced glomerular nitration rate (GFR) without significant reduction of renal blood flow. To investigate the role of pressure gradients in determination of GFR, micropuncture studies were performed in animals 23 ± 3 days of age subjected to left ureteral constriction and right nephrectomy within the first 2 days of life and compared to uninephrectomized controls. Resulting ureteral dilatation was variable, with kidney weight and ureteral diameter being proportional to the rise in ureteral pressure (PU). In individual animals with severe CPUO (ureteral diameter > 3 mm), distal tubular transit time was either normal (31-90 s) or prolonged ( > 120 s). Superficial single nephron GFR (SNGFR) was inversely correlated with PU. Glomerular capillary pressure and afferent arteriolar colloid oncotic pressure were not affected by CPUO while peritubular capillary, proximal and distal intratubular hydrostatic pressure increased as a function of Pu. As a result, afferent effective filtration pressure (EFPA) was reduced in severe (10.0 ± 1.1 mm Hg) compared to mild CPUO (13.4 ± 0.5 mm Hg), but was not different from controls (11.3 ± 0.9 mm Hg). For both control and CPUO groups, superficial SNGFR increased by 0.5 nl/min for each mm Hg increase in EFPA but for a given EFPA, SNGFR was 6 nl/min lower in guinea pigs with CPUO. These results indicate that higher EFPA in animals with mild compared to severe CPUO contributes to maintenance of higher SNGFR. However, a 70% reduction in superficial SNGFR for guinea pigs with severe CPUO is due in large part to reduced ultrafiltration coefficient. The mechanisms whereby chronically elevated PU in the neonate result in these complex changes of glomerular dynamics may relate to altered intrarenal production of vasoactive hormones.

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