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Updated: May 8, 2026
Getting to Compliance in Forced Exercise in Rodents: A Critical Standard to Evaluate Exercise Impact in Aging-related Disorders and Disease
Published on: August 22, 2014
Effect of age and exercise training on protein:protein interactions among eNOS and its regulatory proteins in rat
Meredith J Luttrell1, John W Seawright, Emily Wilson
1Department of Health and Kinesiology, Texas A&M University, MS 4243, College Station, TX, 77843-4243, USA.
Purpose:
We tested the hypothesis that impaired endothelium-dependent relaxation in aged aorta is due, in part, to altered protein:protein interactions between endothelial nitric oxide synthase (eNOS) and key regulatory proteins resulting in impaired nitric oxide (NO)-mediated relaxation. We also hypothesized that endurance exercise training improves or restores NO-mediated vasorelaxation in aged aorta by reversing the detrimental effects of aging on protein:protein interaction between eNOS and its key regulatory proteins.
Methods:
Young (2 month) and old (22 month) rats were exercise trained (Ex) or remained sedentary (Sed) for 10 weeks yielding four groups of rats: (1) young Sed, (2) young Ex, (3) old Sed, and (4) old Ex. Endothelium-dependent relaxation to acetylcholine (ACh) and protein:protein interactions were assessed in aortas. To determine the role of eNOS, endothelium-dependent relaxation to ACh was assessed in the presence of L-NAME. Protein:protein interactions were assessed using co-immunoprecipitation.
Results:
Acetylcholine-induced relaxation was impaired in OldSed relative to YoungSed aortas. Training restored ACh-induced vasorelaxation responses so that OldEx were not different from YoungSed. L-NAME abolished the effects of age and exercise training on ACh-induced relaxation responses. Aging resulted in lower Cav1:eNOS and CaM:eNOS interactions but had no effect on Hsp90:eNOS interaction. Exercise training did not alter protein:protein interactions.
Conclusion:
Nitric oxide-mediated, endothelium-dependent relaxation is impaired in old aorta, which is associated with reduced Cav1:eNOS and CaM:eNOS interactions. Exercise training restores endothelium-dependent relaxation in old aortas by enhancing NO-mediated vasorelaxation. The beneficial effect of training is not mediated by reversing the detrimental effects of aging on protein:protein interactions between eNOS and its key regulatory proteins.
