DURATION AND MECHANISMS OF THE INCREASED NATURAL CYTOTOXICITY SEEN AFTER CHRONIC VOLUNTARY EXERCISE IN RATS

We have recently shown that in vivo natural cytotoxicity is enhanced a fter chronic exercise in spontaneously hypertensive rats (SHRs). In th e present report, we have studied the duration of this augmentation an d some possible mechanisms involved. Exercise consisted of voluntary r unning for 4-5 weeks, with the running distance ranging from 2.7-15.6 km day(-1) during the last week of running. in vivo cytotoxicity was m easured as clearance of injected Cr-51-labelled YAC-1 lymphoma cells f rom the lungs. The in vivo natural cytotoxicity was increased in runni ng SHRs, and also in SHRs that had their running wheel locked for 24 a nd 48 h prior to the experiment, and was still present after 96 h. The enhancement of in vivo cytotoxicity after 5 weeks of exercise was abo lished after an acute injection of the P-adrenergic receptor antagonis t timolol (0.5 mg kg(-1) i.v.), indicating that catecholamines are inv olved in this augmentation. interestingly. 24 h after the last exercis e bout, the increased natural cytotoxicity could be blocked by timolol . The opioid receptor antagonist naloxone given subcutaneously for 7 d ays by osmotic pumps (6 mg kg(-1) h(-1)) could not reverse the increas ed in vivo cytotoxicity seen in the running SHRs, suggesting that opio id receptor mechanisms are not involved, or at least not the naloxone- sensitive mu-receptor. Natural immunity was not influenced by the hist amine H-2 receptor antagonist ranitidine. either in controls or in run ners, indicating that the natural killer cell-regulatory effect of his tamine is not present in SHRs and does not seem to be involved in the exercise-induced changes in natural immune function. We conclude that the augmentation of in vivo natural cytotoxicity after voluntary chron ic exercise in rats is long-lasting and that the augmentation is partl y mediated by beta-adrenergic receptors.