INCREASED SCIATIC-NERVE BLOOD-FLOW IN DIABETIC RATS - ASSESSMENT BY MOLECULAR VS PARTICULATE MICROSPHERES

Sciatic nerve blood flow in diabetic rats is typically increased or un changed when assessed by the reference sample microsphere method in ou r laboratory In contrast, blood flow is generally reported to be decre ased similar to 50% when assessed with laser Doppler flowmetry or hydr ogen clearance polarography. To address concerns that increased blood flow observed with microspheres might be anomalous because of their pa rticulate nature and/or because insufficient numbers of microspheres a re captured in the nerve, a plasma-soluble ''molecular microsphere'' ( [H-3]desmethylimipramine, mol mt = 266) and 11.3-mu m Gd-153-labeled m icrospheres were injected sequentially to assess blood flow in rats wi th streptozotocin diabetes of 2-4 wk duration. Nerve blood flows in di abetic rats were increased 1.5- to 2-fold (vs. control rats) with both tracers; these increases were prevented by tolrestat, an inhibitor of aldose reductase. These observations indicate that blood flow in scia tic nerve (like that in retina and kidney) is increased early after th e onset of diabetes and is 1) demonstrable with a plasma-soluble trace r as well as with particulate microspheres and 2) linked to increased metabolism of glucose via the sorbitol pathway.