Sorbinil prevents glomerular hyperperfusion in diabetic rats.

Area of Science:

• Nephrology
• Endocrinology
• Metabolic Research

Background:

• Insulin-dependent diabetes mellitus (IDDM) is associated with glomerular hyperperfusion.
• The polyol pathway is implicated in diabetic complications.
• Aldose reductase plays a key role in the polyol pathway.

Purpose of the Study:

• To investigate the role of polyol pathway metabolism in diabetic glomerular hyperperfusion.
• To assess the effect of aldose reductase inhibition on renal hemodynamics in IDDM.

Main Methods:

• Streptozotocin-induced diabetic rat model.
• Administration of aldose reductase inhibitor (sorbinil).
• Micropuncture techniques to measure single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF).
• Measurement of plasma renin activity (PRA) and glomerular angiotensin II (ANG II)-receptor sites.

Main Results:

• Diabetic rats exhibited increased SNGFR, QA, SNBF, and reduced afferent resistance.
• Glomerular ANG II-receptor sites were decreased in untreated diabetic rats.
• Sorbinil treatment normalized SNGFR, QA, and SNBF in diabetic rats.
• Sorbinil did not affect PRA, glomerular ANG II receptors, or blood glucose levels.
• Single-nephron filtration fraction (SNFF) increased above normal in sorbinil-treated diabetic rats.

Conclusions:

• Polyol pathway metabolism contributes significantly to glomerular hyperperfusion in IDDM.
• Inhibition of aldose reductase normalizes hyperfiltration by increasing vascular smooth muscle tone.
• Aldose reductase inhibition represents a potential therapeutic strategy for diabetic nephropathy.