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Voluntary Exercise Attenuates Reactive Oxygen Species Mediated Endothelial Dysfunction in Rodents Fed a High Sodium Diet Independent of Blood Pressure
Author(s) -
Guers John J.,
KaseckyLardner Lauren,
Farquhar William B.,
Edwards David G.,
LenEdwards Shan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1287.10
Subject(s) - apocynin , endocrinology , medicine , chemistry , reactive oxygen species , sodium , aerobic exercise , nitric oxide , nadph oxidase , blood pressure , biochemistry , organic chemistry
High sodium diets have been shown to cause endothelial dysfunction and diminish nitric oxide bioavailability independent of blood pressure (BP). This deleterious effect has been linked to increases in reactive oxygen species (ROS). Exercise is known for its beneficial effect on endothelial function. This may be due, in part, to a reduction in ROS production. The purpose of this study was to test the hypothesis that voluntary wheel running prevents the deleterious effect of high sodium on endothelial function by reducing ROS independent of BP. Eight week old male Sprague‐Dawley rats were placed on either a normal sodium (NS, 0.4%) or high sodium (HS, 4.0%) diet for 6 weeks. Diet groups were further subdivided into a sedentary (NS, HS) or exercise group (NS‐EX, HS‐EX), the latter were placed in a cage with 24‐hour access to a running wheel. BP was measured 3 times per week and did not change in any group. Blood and urine were collected at baseline and 6 weeks in order to assess serum and urinary sodium. Animals were sacrificed after 6 weeks and endothelium‐dependent relaxation (EDR) was assessed by dose response to acetylcholine (ACh), in the presence and absence of the superoxide scavenger tempol and the NADPH oxidase inhibitor apocynin (Apo) in femoral rings. Citrate synthase (CS) activity was measured in the soleus muscle. Serum and urinary sodium concentrations were elevated in HS groups relative to NS (p<0.05). CS activity was greater in both exercise groups indicating a training effect (p < 0.05). Femoral EDR was reduced in HS (n=11) compared to NS (n=10) rats as demonstrated by an attenuated maximal response (Emax: HS, 39.4% ± 4.8 vs. NS, 66.9% ± 3.9; p < 0.05). Emax was improved by tempol (HS+T, 65.9% ± 5.6; p <0.05) and Apo (HS+Apo, 62.9% ± 10.9; p <0.05) compared to HS alone. Total EDR as assessed by area under the curve (AUC) increased in HS animals with the addition of tempol but did not quite reach significance (AUC: HS, 63.8% ± 8.1 vs. HS+T, 89.6% ± 8.02; p=0.06). Exercise rescued Emax in the presence of a HS diet (HS‐EX (n=8), 76.8% ± 7.3 vs. HS, 39.4% ± 4.8; p<0.05) and AUC (AUC: HS‐EX, 127.1% ± 0.1 vs. HS, 63.8% ± 8.1; p <0.05). The addition of tempol and/or Apo had negative effects in general on EDR in the exercise groups. AUC was diminished in the HS‐EX group with the addition of tempol (p<0.05), while the administration of Apo decreased AUC in NS‐EX (n=10) (p < 0.05). Both tempol and apocynin decreased Emax significantly in NS‐EX animals. In conclusion, HS impairs EDR through NADPH oxidase meditated ROS. Voluntary wheel running restored EDR likely through a reduction in ROS. EDR was diminished in the exercising groups with the addition of antioxidants suggesting there may be a critical level of ROS needed for maintenance of normal vascular functioning. Support or Funding Information ACSM Foundation Research Grant