BackgroundPhysical activity can reduce sympathetic tone and may be beneficial to human health. Whether the vascular responses to norepinephrine (NE), an adrenergic vasocon-strictor, could be altered by chronic exercise was unclear. We therefore conducted this study to investigate the effects of endurance exercise training on NE-induced vasoconstrictive response in healthy rabbits. Possible mechanisms were also studied.Methods and ResultsTwenty-four male New Zealand White rabbits were used for this study. They were divided into two groups: control and training. The training group was trained on a treadmill with running speed of 0.88 km/h at a 0° grade for 10 to 60 minutes per day, for 5 days a week for a total of 8 weeks. At the end of the experiments, thoracic aortae (3 mm long) were isolated. The vascular tension was measured with a force transducer. The dose-response relation of NE-induced vasoconstriction was determined and compared for control (n=5) and trained (n=6) groups. To verify the possible involvement of endothelium-derived relaxing factor (EDRF) in the alteration of NE-induced vasoconstriction after exercise training, we compared the vascular responses to NE in endo-thelium- intact,Nω-nitro-L-arginine (L-NNA, 10−4mol/L)-pre-treated, or denuded vessel segments (n=4 for each experiment of each group). EDRF release in the presence or absence of NE was also evaluated by the increased tension induced by hemoglobin (10−5mol/L), an EDRF scavenger (n=6 for the control group and n=8 for the trained group). In addition, vascular responses to some specific adrenergic agonists (ie, phenylephrine, an α1-agonist, and clonidine, an α2-agonist) were also studied to see if a specific adrenergic receptor was involved (n=4 for each experiment of each group). Our results indicated that (1) [NE]ED50of the thoracic aorta was elevated by exercise training; (2) in the presence of NE, EDRF release from the thoracic aorta, assessed by addition of hemoglobin or L-NNA, was higher in the trained group than in the control group; (3) both phenylephrine (10−8mol/L) and clonidine (10−6mol/L) could evoke vasorelaxation that would be inhibited by L-NNA; and (4) in addition to causing vasoconstriction, NE could stimulate EDRF release, possibly via α1- and α2-receptors of endothelial cells.ConclusionsOur data suggest that exercise training may decrease NE-induced vasoconstrictive response and may increase NE-stimulated EDRF release.