PHYSICAL CONDITIONING DECREASES NOREPINEPHRINE-INDUCED VASOCONSTRICTION IN RABBITS - POSSIBLE ROLES OF NOREPINEPHRINE-EVOKED ENDOTHELIUM-DERIVED RELAXING FACTOR

Background Physical activity can reduce sympathetic tone and may be be neficial to human health. Whether the vascular responses to norepineph rine (NE), an adrenergic vasoconstrictor, could be altered by chronic exercise was unclear. We therefore conducted this study to investigate the effects of endurance exercise training on NE-induced vasoconstric tive response in healthy rabbits. Possible mechanisms were also studie d. Methods and Results Twenty-four male New Zealand White rabbits were used for this study. They were divided into two groups: control and t raining. The training group was trained on a treadmill with running sp eed of 0.88 km/h at a 0 degrees grade for 10 to 60 minutes per day, fo r 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 m easured with a force transducer. The dose-response relation of NE-indu ced vasoconstriction was determined and compared for control (n=5) and trained (n=6) groups. To verify the possible involvement of endotheli um-derived relaxing factor (EDRF) in the alteration of NE-induced vaso constriction after exercise training, we compared the vascular respons es to NE in endothelium-intact, N-omega-nitro-L-arginine (L-NNA, 10(-4 ) mol/L)-pretreated, or denuded vessel segments (n=4 for each experime nt of each group). EDRF release in the presence or absence of NE was a lso evaluated by the increased tension induced by hemoglobin (10(-5) m ol/L), an EDRF scavenger (n=6 for the control group and n=8 for the tr ained group). In addition, vascular responses to some specific adrener gic agonists (ie, phenylephrine, an alpha(1)-agonist, and clonidine, a n alpha(2)-agonist) were also studied to see if a specific adrenergic receptor was involved (n=4 for each experiment of each group). Our res ults indicated that (1) [NE](ED50) of 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 high er in the trained group than in the control group; (3) both phenylephr ine (10(-8) mol/L) and clonidine (10(-6) mol/L) could evoke vasorelaxa tion that would be inhibited by L-NNA; and (4) in addition to causing vasoconstriction, NE could stimulate EDRF release, possibly via alpha( 1)- and alpha(2)-receptors of endothelial cells. Conclusions Our data suggest that exercise training may decrease NE-induced vasoconstrictiv e response and may increase NE-stimulated EDRF release.