title: Voluntary wheel running augments aortic l-arginine transport and endothelial 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 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 ⅚ 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 < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 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-[(3)H]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.
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware;
authors: Christopher R
authors: CR
authors: Martens
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware; Department of Biological Sciences, University of Delaware, Newark, Delaware; and.
authors: James M
authors: JM
authors: Kuczmarski
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware;
authors: Jahyun
authors: J
authors: Kim
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware;
authors: John J
authors: JJ
authors: Guers
authors: Department of Kinesiology and Health Sciences, The College of William and Mary, Williamsburg, Virginia.
authors: M Brennan
authors: MB
authors: Harris
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware; Department of Behavioral Health and Nutrition, University of Delaware, Newark, Delaware;
authors: Shannon
authors: S
authors: Lennon-Edwards
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware; Department of Biological Sciences, University of Delaware, Newark, Delaware; and dge@udel.edu.
authors: David G
authors: DG
authors: Edwards
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D026923:Amino Acid Transport Systems, Basic / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D012420:Running; D014664:Vasodilation / Q000187:drug effects
chemical_list: D026923:Amino Acid Transport Systems, Basic; D001120:Arginine; D000109:Acetylcholine
keywords: chronic kidney disease; endothelial dysfunction; exercise; l-arginine