Spier Scott A, Delp Michael D, Stallone John N, Dominguez James M, Muller-Delp Judy M
Department of Health and Kinesiology, University of Texas at Tyler, Tyler, TX, USA.
Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3119-27. doi: 10.1152/ajpheart.00588.2006. Epub 2007 Mar 2.
Flow-induced vasodilation is attenuated with old age in rat skeletal muscle arterioles. The purpose of this study was to determine whether diminished cyclooxygenase (COX) signaling contributes to the age-induced attenuation of flow-induced vasodilation in gastrocnemius muscle arterioles and to determine whether, and through which mechanism(s), exercise training restores this deficit in old rats. Fischer 344 rats (3 and 22 mo old) were assigned to a sedentary or exercise-trained group. First-order arterioles were isolated from the gastrocnemius muscles, cannulated, and pressurized to 70 cm H(2)O. Diameter changes were determined in response to graded increases in intraluminal flow in the presence and absence of nitric oxide synthase (NOS) inhibition [10(-5) M N(G)-nitro-L-arginine methyl ester (L-NAME)], COX inhibition (10(-5) M indomethacin), or combination NOS (10(-5) M L-NAME) plus COX (10(-5) M indomethacin) inhibition. Aging reduced flow-induced vasodilation in gastrocnemius muscle arterioles. Exercise training restored responsiveness to flow in arterioles of aged rats and enhanced flow-induced vasodilation in arterioles from young rats. L-NAME inhibition of flow-induced vasodilation was greater in arterioles from old rats compared with those from young rats and was increased after exercise training in arterioles from both young and old rats. Although the indomethacin-sensitive portion of flow-induced dilation was not altered by age or training, both COX-1 mRNA expression and PGI(2) production increased with training in arterioles from old rats. These data demonstrate that exercise training restores flow-induced vasodilation in gastrocnemius muscle arterioles from old rats and enhances flow-induced vasodilation in gastrocnemius muscle arterioles from young rats. In arterioles from both old and young rats, the exercise training-induced enhancement of flow-induced dilation occurs primarily through a NOS mechanism.
在大鼠骨骼肌小动脉中，血流诱导的血管舒张作用会随着年龄增长而减弱。本研究的目的是确定环氧化酶（COX）信号减弱是否导致老年大鼠腓肠肌小动脉中血流诱导的血管舒张作用减弱，以及确定运动训练是否能恢复老年大鼠的这一缺陷，以及通过何种机制恢复。将Fischer 344大鼠（3月龄和22月龄）分为久坐组或运动训练组。从腓肠肌中分离出一级小动脉，插管并加压至70 cm H₂O。在存在和不存在一氧化氮合酶（NOS）抑制[10⁻⁵ M N⁻硝基-L-精氨酸甲酯（L-NAME）]、COX抑制（10⁻⁵ M吲哚美辛）或联合NOS（10⁻⁵ M L-NAME）加COX（10⁻⁵ M吲哚美辛）抑制的情况下，测定随着管腔内血流分级增加而引起的直径变化。衰老会降低腓肠肌小动脉中血流诱导的血管舒张作用。运动训练恢复了老年大鼠小动脉对血流的反应性，并增强了年轻大鼠小动脉中血流诱导的血管舒张作用。与年轻大鼠的小动脉相比，L-NAME对老年大鼠小动脉中血流诱导的血管舒张作用的抑制作用更强，并且在年轻和老年大鼠的小动脉运动训练后均增加。尽管血流诱导舒张的吲哚美辛敏感部分不受年龄或训练的影响，但老年大鼠小动脉中COX-1 mRNA表达和PGI₂产生均随着训练而增加。这些数据表明，运动训练可恢复老年大鼠腓肠肌小动脉中血流诱导的血管舒张作用，并增强年轻大鼠腓肠肌小动脉中血流诱导的血管舒张作用。在老年和年轻大鼠的小动脉中，运动训练诱导的血流诱导舒张增强主要通过NOS机制发生。
