Glomerular and tubular adaptive responses to acute nephron loss in the rat. Effect of prostaglandin synthesis inhibition.
These studies, using in vivo micropuncture techniques in the Munich-Wistar rat, document the magnitude of changes in glomerular and tubular function and structure 24 h after approximately 75% nephron loss (Nx) and compared these results with those obtained in sham-operated rats. The contribution of either nephron hypertrophy or renal prostaglandin to these adjustments in nephron function was also explored. After acute Nx, single nephron GFR (SNGFR) was increased, on average by approximately 30%, due primarily to glomerular hyperperfusion and hypertension. The approximately 45% reduction in preglomerular and the constancy in postglomerular vascular resistances was entirely responsible for these adaptations. Although increases in fluid reabsorption in proximal convoluted tubules correlated closely with increase in SNGFR, the fractional fluid reabsorption between late proximal and early distal tubular segments was depressed. Nephron hypertrophy could not be substantiated based on either measurements of protein content in renal tissue homogenates or morphometric analysis of proximal convoluted tubules. However, acute Nx was associated with increased urinary excretory rates per functional nephron for 6-keto-PGF1 alpha and TXB2. Prostaglandin synthesis inhibition did not affect function in control nephrons, but this maneuver was associated with normalization of glomerular and tubular function in remnant nephrons. The results suggest that enhanced synthesis of cyclooxygenase-dependent products is one of the earliest responses to Nx, and even before hypertrophy the pathophysiologic effects of prostaglandin may be important contributors to the adaptations in remnant nephron function.
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
J C
JC
Pelayo
P F
PF
Shanley
D000222:Adaptation, Physiological; D000818:Animals; D004247:DNA / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006400:Hematocrit; D006439:Hemodynamics; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D009392:Nephrectomy; D011453:Prostaglandins / Q000502:physiology* / Q000652:urine; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014882:Water-Electrolyte Balance
D011453:Prostaglandins; D011506:Proteins; D012313:RNA; D004247:DNA; D007213:Indomethacin