Capillary Basement Membrane Thickness and Capillary Density in Sedentary and Trained Obese Zucker Rats

The purpose of this study was to determine whether the obese Zucker rat (OZR) develops diabeteslike peripheral vascular disease and evaluate the effects of exercise training (treadmill running, 15 m/min, 17% grade, 60 min/day, 5 days/wk, for 6 or 12 wk) on skeletal muscle vascular disease. Capillary density (CD) and capillary basement membrane (CBM) thickness were measured in the plantar muscle of sedentary and trained OZR and sedentary lean Zucker rats (LZRs). At 11 wk old, when profoundly obese, hyperinsulinemic, and insulin resistant, OZRs had lower CD and thicker CBM than LZRs. These characteristics are consistent with the expression of human diabetic microangiopathy and imply altered diffusion capacity due to increased diffusion distance and changes in the capillary wall. Between 11 and 18 wk of age, OZRs became hyperglycemic. No age-related changes in CD were observed in lean or obese animals, and OZRs had lower CDs than LZRs at 18 wk of age. CBM thickness decreased from 11 to 18 wk of age in both lean and obese animals, but the decline was proportionally greater in OZRs, and the CBM of obese animals was only slightly thicker than in lean 18-wk-old animals. Exercise training did not alter CD or CBM thickness in 11-wk-old animals. In contrast, training for 6 or 12 wk increased both CD and CBM thickness in 18-wk-old animals, normalizing CD but further increasing CBM thickness relative to LZRs. Correlational analysis revealed that CBM thickness is related to basal insulin concentration (r = .29, P <.05) but not to basal glucose (r = .12, P >.05). No relationship was evident for CD. OZRs have fewer capillaries and thicker CBM in skeletal muscle at 11 and 18 wk of age. In addition, exercise training may improve skeletal muscle diffusion capacity in OZRs by stimulating capillary proliferation; however, microvascular function may be further compromised by additional thickening of the CBM. The effects of exercise training on CBM thickness may depend on the corresponding changes in the basal insulin concentration.