Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor L-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent 5/6 ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN + ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 +/- 9.01 vs 100 +/- 4.58, P \u3c 0.05) and reduced maximal response (E-max; 59.9 +/- 9.67 vs. 94.31 +/- 1.27%, P \u3c 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUN + ARG-treated animals. Maximal relaxation was elevated above SED in RUN + ARG animals only. L-[H-3] arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN + ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with L-arginine
