ABSTRACT
The role of polyol pathway metabolism in glomerular hyperperfusion of insulin-dependent diabetes mellitus (IDDM) was studied in rats. Streptozotocin-induced diabetic rats were fed the aldose reductase inhibitor, sorbinil (8 mg/day). Untreated diabetic rats and normal rats served as controls. All groups were fed the same diet, rationed to 20 g/day. Micropuncture, plasma renin activity (PRA), and glomerular angiotensin II (ANG II)-receptor measurements were made 7-15 days after streptozotocin injection. Untreated diabetic rats had higher than normal single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF), and reduced afferent resistance. Glomerular ANG II-receptor sites were markedly decreased. In diabetic rats fed sorbinil SNGFR, QA, and SNBF were all lower than in untreated diabetic rats, and indistinguishable from values in normal rats. However, single-nephron filtration fraction (SNFF) rose above normal. PRA, glomerular ANG II receptors, and blood glucose were not affected by sorbinil. In normal rats fed sorbinil, SNGFR, QA, and SNBF were not significantly different than in normal rats. Our observations are consistent with the view that polyol pathway metabolism plays a role in glomerular hyperperfusion in IDDM. Inhibition of aldose reductase increased vascular smooth muscle tone at pre- and probably postglomerular sites.
Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/prevention & control , Imidazoles/pharmacology , Imidazolidines , Kidney Glomerulus/pathology , Sugar Alcohol Dehydrogenases/antagonists & inhibitors , Animals , Blood Pressure/drug effects , Hemodynamics/drug effects , Kidney Glomerulus/drug effects , Kidney Glomerulus/physiopathology , Male , Mathematics , Models, Theoretical , Rats , Rats, Inbred Strains , Reference ValuesABSTRACT
A case-control study was conducted to investigate possible environmental risk factors for ocular sarcoidosis. The factors studied were exposures to pine products and occupational histories of employment in the tobacco, lumber, and textile industries. The exposure histories of 29 female and 15 male cases, patients with newly diagnosed ocular sarcoidosis that were attending the Glaucoma/Uveitis Clinic of the North Carolina Memorial Hospital, were compared to those of 110 female and 28 male controls selected from out-patient clinics. Elevated risks for sarcoidosis were detected among those females that were exposed to burning pine or were employed in the tobacco industry. For males, positive associations were observed for chewing pine products and for employment in the lumber and textile industries. These preliminary data are consistent with incomplete phagocytic clearance of nonbiodegradable foreign bodies present within our environment that may become antigenic to the immunologically susceptible host. Confirmation of refutation of these hypotheses awaits additional clinical and epidemiological research within the sarcoidosis belt.
