Circadian changes in renal hemodynamics and urinary glycosaminoglycan (GAG) excretion were studied in normal Sprague-Dawley rats to further investigate rhythms in kidney function. Urinary water, protein, and GAG excretion, as well as glomerular filtration rate (GFR) and renal plasma flow (RPF), were determined every 4h over the 24h cycle in an attempt to characterize any temporal changes. Urinary flow rate and proteinuria peaked during the dark activity period of the animals, consistently at the same hour, whereas the lowest values were detected during the resting phase. GAG are mucopolysaccharides entering the constitution of the glomerular basement membrane (GBM), which is the key component in the process of glomerular filtration. Similarly, the urinary excretion rate of GAG showed a circadian rhythmicity in phase with urinary water and protein excretion, with markedly increased values observed during the nocturnal phase of the animals. Moreover, GFR and RPF were demonstrated to exhibit large circadian variations in phase with renal excretory rhythmicity, showing nighttime values significantly greater compared to daytime ones. Strong correlations were found between GFR and RPF rhythms, as well as between GAG and GFR, and GAG and RPF rhythms, although the latter were not statistically significant. This pattern suggests that the circadian rhythmicity in urinary excretion rate of GAG in physiological conditions could presumably be secondary to the temporal changes in renal hemodynamics. In this respect, knowledge of renal chronobiology helpfully contributes to increase our understanding of renal physiology.
Subtotal nephrectomy in the rat is followed by early hypertrophy and functional adaptation of the remnant glomeruli in which mesangial cells seem to play a leading part. Using a morphoquantitative approach, we assessed the vasoconstrictive response to 1 μM cyclosporin A (CsA) or 0.1 μM angiotensin II (All) of isolated glomeruli and cultured mesangial cells obtained from normal rats and from rats after five-sixths nephrectomy. In normal rats, a significant reduction of glomerular size was observed after the administration of vasoactive agents (-14% after 30min exposure to CsA or All). After five-sixths nephrectomy the vasoconstrictive response, which was preserved at the 4th hour (-12% at the 30th minute), disappeared at the 24th hour (-1.5% at the 30th minute), but was maintained in animals pretreated with indomethacin (-10% at the 30th minute). Similar responses were observed with cultured mesangial cells at the first passage. Inhibition of prostaglandin synthesis abolishes the adaptative adjustments observed in partially nephrectomized rats during the first days after surgery. These findings suggest that renal vasodilatory prostaglandins may participate in the compensatory hemodynamic adjustments following subtotal nephrectomy.
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