Exercise Training Augments Flow-Dependent Dilation in Rat Skeletal Muscle Arterioles

Abstract

We aimed to test the hypothesis that as a consequence of short-term daily exercise, flow (shear stress)–dependent dilation and its mediation by the endothelium are altered in skeletal muscle arterioles. After initial familiarization with the protocol, rats ran on a treadmill once a day (with gradually increasing intensity up to 40 minutes and 28 m/min) for ≈3 weeks (EX group); a control group remained sedentary (SED group). The active (internal) diameters of isolated gracilis muscle arterioles of SED and EX rats at 80 mm Hg were significantly different (55.2±2.1 and 49.3±2.0 μm, P<.05), and their passive diameters (in Ca²⁺-free solution) were 105.3±3.1 and 111.2±2.4 μm (not significantly different), respectively. Increases in flow of the perfusion solution from 0 to 12 μL/min elicited a significantly greater increase in diameter of EX arterioles (by 83.5% at maximum flow). This enhanced sensitivity maintained a lower shear stress in EX arterioles (15 to 20 dyne/cm²) compared with SED arterioles (25 to 35 dyne/cm²). In both SED and EX arterioles, flow-dependent dilation was eliminated after removal of the endothelium. Either N^ω-nitro-l-arginine, a nitric oxide synthase inhibitor, or indomethacin, an inhibitor of prostaglandin synthesis, shifted the flow-diameter and calculated wall shear stress–diameter curves significantly to the right. Each of the inhibitors reduced flow-dependent dilation to a similar degree (≈40% to 45%); their combined administration nearly completely eliminated the dilation of arterioles of both SED and EX rats. Thus, we conclude that the sensitivity of gracilis muscle arterioles of rats to wall shear stress is upregulated after short-term daily exercise, resulting in an augmented dilator response that is due to an increased release of both endothelium-derived nitric oxide and prostaglandins.