Experimental dietary galactosemia is known to result in accumulation of the polyol, galactitol, via the aldose reductase metabolic pathway in a variety of tissues, including renal glomeruli. Because increased polyol accumulation also occurs in insulin-dependent diabetes mellitus (IDDM), in which marked renal glomerular hyperperfusion occurs, we have studied glomerular hemodynamics in rats with experimental galactosemia. Insulin deficiency and its accompanying metabolic disorders are not present in this experimental model. In additional groups of animals, aldose reductase inhibitors, either sorbinil or tolrestat, were added to the galactose diet. In all, five groups of rats were studied: regular diet, 50% galactose diet, regular diet plus sorbinil, 50% galactose diet plus sorbinil, and 50% galactose plus tolrestat. The diets were comparable in protein and salt, and the rats were pair fed. Micropuncture and whole kidney clearance measurements were carried out after 10-14 days on these diets. Compared with rats fed the regular diet, those fed with 50% galactose diet had significantly higher glomerular filtration rates, renal plasma flow, single-nephron glomerular filtration rates, and plasma flow (Q(A)), whereas afferent vascular resistance (R(A)) was decreased. Addition of sorbinil or tolrestat to the high-galactose diet not only prevented renal hyperperfusion but R(A) and single-nephron filtration fraction (SNFF) were higher than in normal rats, and Q(A) was lower. In addition, sorbinil administration to rats on the control diet caused significant decreases in single-nephron blood flow and the ultrafiltration coefficient and a rise in SNFF. These observations are consistent with the view that metabolic abnormalities linked to increased polyol pathway metabolism in experimental galactosemia lead to reduced renal vascular resistance and to glomerular hyperfusion. Similar metabolic disturbances may play a role in the glomerular hyperperfusion of early IDDM.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - Jan 1 1989|
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