Microcirculatory structure-function relationships in skeletal muscle of diabetic rats

Document Type

Article

Publication Title

American Journal of Physiology - Heart and Circulatory Physiology

Abstract

The effects of streptozotocin-induced diabetes on microcirculatory structure-function relationships in skeletal muscle were studied in control (C) and diabetic (D; 65 mg/kg streptozotocin ip) rats 6-8 wk after injection. Capillary exchange capacity was determined from measurements of capillary filtration coefficient (CFC) and permeability-surface area product (PS) for 51Cr-labeled EDTA in maximally vasodilated (papaverine), isolated hindquarters of C (n = 9) and D (n = 12) rats. Capillary numerical density, length, surface area, capillary geometry, and muscle fiber cross-sectional area were determined using morphometric methods 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) weighed less than C rats (90 ± 3 g) because of marked muscle atrophy. Minimal total vascular resistance was lower in D rats (P ≤ 0.05), indicating an increased flow capacity. CFC was not different 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 flow was depressed in D rats (P ≤ 0.05) compared with C rats, which indicated a reduced capillary diffusing capacity. Plantaris muscle weight was 41% less in D rats (174 ± 9 vs. 293 ± 11 mg; P ≤ 0.001). Morphometric analysis revealed that muscle fiber cross-sectional area was reduced 39% in D rats, which, despite a lower capillary-to-fiber ratio (1.59 ± 0.04 vs. 2.12 ± 0.13; P ≤ 0.001), resulted in a 27% increase in capillary density in D rats. Capillary diameter was less in D rats (3.58 ± 0.12 vs. 4.51 ± 0.23 μm; P ≤ 0.005). Total capillary surface area was per muscle fiber volume was unchanged in D rats (231 ± 34 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 reduction in total microvascular surface area. The reduction in capillary surface area is proportional to the degree of muscle atrophy in D rats such that functional microvascular surface area per tissue mass (e.g., CFC) is unchanged. The lower diffusing capacity (PS) in D rats suggests that either small solute permeability is reduced and/or there is greater perfusion heterogeneity in D rat skeletal muscle.

DOI

10.1152/ajpheart.1994.266.4.h1502

Publication Date

1-1-1994

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