Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism

Functional sympatholysis is impaired in hypertensive animals and patients. Exercise training (ET) improves functional sympatholysis through a nitric oxide (NO)-dependent mechanism in normotensive rats. However, whether ET has similar physiological benefits in hypertension remains to be elucidated. Thus we tested the hypothesis that the impairment in functional sympatholysis in hypertension is reversed by ET through a NO-dependent mechanism. In untrained normotensive Wistar-Kyoto rats (WKY_UT; n = 13), untrained spontaneously hypertensive rats (SHR_UT; n = 13), and exercise-trained SHR (SHR_ET; n = 6), changes in femoral vascular conductance (FVC) were examined during lumbar sympathetic nerve stimulation (1, 2.5, and 5 Hz) at rest and during muscle contraction. The magnitude of functional sympatholysis (Δ%FVC = Δ%FVC muscle contraction - Δ%FVC rest) in SHR_UT was significantly lower than WKY_UT (1 Hz: -2 ± 4 vs. 13 ± 3%; 2.5 Hz: 9 ± 3 vs. 21 ± 3%; and 5 Hz: 12 ± 3 vs. 26 ± 3%, respectively; P < 0.05). Three months of voluntary wheel running significantly increased maximal oxygen uptake in SHR_ET compared with nontrained SHR_UT (78 ± 6 vs. 62 ± 4 ml·kg-1·min-1, respectively; P < 0.05) and restored the magnitude of functional sympatholysis in SHR_ET (1 Hz: 9 ± 2%; 2.5 Hz: 20 ± 4%; and 5 Hz: 34 ± 5%). Blockade of NO synthase (NOS) by NG-nitro-L-arginine methyl ester attenuated functional sympatholysis in WKY_UT but not SHR_UT. Furthermore, NOS inhibition significantly diminished the improvements in functional sympatholysis in SHR_ET. These data demonstrate that impairments in functional sympatholysis are normalized via a NO mechanism by voluntary wheel running in hypertensive rats.