MICROCIRCULATORY STRUCTURE-FUNCTION-RELATIONSHIPS IN SKELETAL-MUSCLE OF DIABETIC RATS

The effects of streptozotocin-induced diabetes on microcirculatory str ucture-function relationships in skeletal muscle were studied in contr ol (C) and diabetic (D; 65 mg/kg streptozotocin ip) rats 6-8 wk after injection. Capillary exchange capacity was determined from measurement s of capillary filtration coefficient (CFC) and permeability-surface a rea product (PS) for Cr-51-labeled EDTA in maximally vasodilated (papa verine), isolated hindquarters of C (n = 9) and D (n = 12) rats. Capil lary numerical density, length, surface area, capillary geometry, and muscle fiber cross-sectional area were determined using morphometric m ethods in perfusion-fixed plantaris muscles from a second series of C (n = 5) and D (n = 6) rats. Hindquarters of D rats (61 +/- 3 g) weighe d less than C rats (90 +/- 3 g) because of marked muscle atrophy. Mini mal total vascular resistance was lower in D rats (P less than or equa l to 0.05), indicating an increased flow capacity. CFC was not differe nt in C and D rats (0.0282 +/- 0.0020 vs. 0.0330 +/- 0.0025 ml.min(-1) .mmHg(-1).100 g(-1), respectively). The relationship between PS and fl ow was depressed in D rats (P less than or equal to 0.05) compared wit h C rats, which indicated a reduced capillary diffusing capacity. Plan taris muscle weight was 41% less in D rats (174 +/- 9 vs. 293 +/- 11 m g; P less than or equal to 0.001). Morphometric analysis revealed that muscle fiber cross-sectional area was reduced 39% in D rats, which, d espite a lower capillary-to-fiber ratio (1.59 +/- 0.04 vs. 2.12 +/- 0. 13; P less than or equal to 0.001), resulted in a 27% increase in capi llary density in D rats. Capillary diameter was less in D rats (3.58 /- 0.12 vs. 4.51 +/- 0.23 mu m; P less than or equal to 0.005). Total capillary surface area was reduced 42% in D rats; however, capillary s urface area per muscle fiber volume was unchanged in D rats (231 +/- 3 4 vs. 237 +/- 16 cm(-1)). These data indicate that there is remodeling of the capillary bed in skeletal muscle of D rats, resulting in a red uction in total microvascular surface area. The reduction in capillary surface area is proportional to the degree of muscle atrophy in D rat s such that functional microvascular surface area per tissue mass (e.g ., CFC) is unchanged. The lower diffusing capacity (PS) in D rats sugg ests that either small solute permeability is reduced and/or there is greater perfusion heterogeneity in D rat skeletal muscle.