Time course of enhanced endothelium-mediated dilation in aorta of trained rats

Previous work has demonstrated that 10 wk of exercise training enhances the responsiveness of rat abdominal aortas to acetylcholine (ACh), an endothelium-dependent vasodilator. The purpose of this study was to determine the time course for this training-induced adaptation of vascular endothelium. Additionally, the contribution of the cyclooxygenase and nitric oxide synthase mechanisms to the enhanced endothelium-mediated relaxation were examined. Male rats were divided into sedentary (SED) and exercise groups. Exercised animals were further subdivided into postexercise (POST-EX), 1 DAY, 1 WK, 2 WK, 4 WK and 10 WK groups. Exercise consisted of treadmill running at 30 m.min-1 (15 degrees incline) for 1 h.d-1 (5 d.wk-1 for the 1 WK, 2 WK, 4 WK, and 10 WK groups). Maximal vasodilator responses induced by 10(-4) M ACh (10(-7) M norepinephrine preconstriction) were determined on abdominal aortic rings in vitro immediately after a single exercise bout in POST-EX rats and 24 h after a single bout of exercise in 1 DAY animals. Maximal 10(-4) M ACh-induced dilation of aortas from 1 WK, 2 WK, 4 WK, and 10 WK animals was determined 24 h after the last exercise bout. Soleus muscle citrate synthase activity was greater in 2 WK (31 +/- 1 mumol.min-1.g wet wt-1), 4 WK (34 +/- 2), and 10 WK (36 +/- 1 mumol.min-1.g wet wt-1) rats than in SED (27 +/- 1 mumol.min-1.g wet wt.-1) animals. Maximal ACh-induced relaxation was greater in aorta from 4 WK (72 +/- 2%) and 10 WK (79 +/- 1%) rats than SED (61 +/- 2%) rats. ACh-mediated dilatory responses remained enhanced in the presence of the cyclooxygenase blocker indomethacin (10(-5) M), but were abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (300 microM). In addition, the expression of endothelial nitric oxide synthase (ecNOS) protein in aortas from 4 WK (P = 0.057) and 10 WK (P < 0.05) rats was greater than in aortas from SED animals. These data indicate that the enhanced endothelium-dependent, ACh-mediated dilation of the rat aorta is present by 4 wk of endurance exercise training. This adaptation appears to be mediated primarily through the nitric oxide synthase pathway and is associated with an increased expression of ecNOS.