Exercise Recovers Loss of Microvessel Density due to Lowered Nitric Oxide Bioavailability

Abstract

Microvessel rarefaction is an indicator of a challenged or disease state in both humans and animal models. The loss of peripheral microvessel density is associated with the metabolic syndrome (MetS). Decreased microvessel density significantly increases the risk for vascular dysfunction and peripheral vascular disease (PVD). Nitric oxide (NO) has been shown to have pro‐angiogenic properties, which suggests that improvement of NO bioavailability in MetS can augment microvessel rarefaction. Exercise, when used as an intervention during MetS, can improve NO bioavailability. The initiating factors for microvessel rarefaction still remain unclear and whether or not exercise can reverse the rarefaction associated with MetS needs to be determined. To examine the correlation between loss in microvessel density and decrease in nitric oxide (NO) bioavailability, capillary to fiber ratio was measured in the soleus and gracilis muscles of obese Zucker rats (OZRs), a model of MetS, and in lean healthy Zucker rats (LZRs). NO levels were measured in stimulated aortas of both groups. OZRs and LZRs were separated into sedentary and exercise training groups (consisting of treadmill running 1 hr/d, 5 d/wk for 8 weeks at 70% of their max running speed). The gracilis arteriole was isolated and then cannulated in a pressurized vessel myobath and exposed to increasing doses of acetylcholine (ACh) to test endothelium‐dependent dilation. Capillary density in the soleus was significantly lower by 15% in OZRs compared to LZRs (p<0.05), and exercise training did not have an effect. In the gracilis, exercise improved capillary density in both OZRs and LZRs. The difference in capillary density between OZR and LZR controls in the gracilis suggest a genotypic disparity. NO bioavailability was significantly decreased in sedentary OZR compared to sedentary LZR, and exercise augmented NO in both groups (p<0.05). Gracilis arteriole dilation response was lower in OZR than LZR (p<0.01) but exercise improved dilation in OZR to almost LZR control values. These results suggest that there is a correlation between decreased NO bioavailability and the loss of peripheral microvessel density, and that exercise may at least partially, depending on the muscle type, reverse this effect and recover arteriole reactivity.Support or Funding InformationThe authors gratefully acknowledge the support by National Institute of Health (5P20GM109098)