The Effect of L‐arginine Supplementation & Voluntary Wheel Running on Vascular Function in Rats with Chronic Kidney Disease

Abstract

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 weeks of voluntary wheel running (RUN) and/or ARG supplementation on vascular function in rats with CKD. 12 week old male Sprague Dawley rats underwent 5/6 ablation infarction surgery to induce CKD, or SHAM surgery as a control. CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined ARG+RUN. Interventions began 4 weeks after surgery to allow time for disease progression. Animals were sacrificed 8 weeks after surgery and endothelium dependent relaxation (EDR) was assessed by dose response to acetylcholine in aortic rings. EDR was significantly impaired in SED vs. SHAM animals after 8 weeks, demonstrated by an attenuated maximal response (Emax; 66.87% ± 6.43 vs 96.79% ± 1.27, p <0.05) and rightward shifted LogEC50 (−6.83 ± 0.08 vs −7.54 ± 0.04, p<0.05). EDR was not significantly improved by ARG or RUN alone, but was improved by combined ARG+RUN (p< 0.05 vs SED). The results suggest a synergistic effect between L‐arginine and exercise that may act as a novel therapy to reduce cardiovascular risk in CKD.Supported by ACSM Foundation Grant