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

Abstract

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 (WKYUT; n = 13), untrained spontaneously hypertensive rats (SHRUT; n = 13), and exercise-trained SHR (SHRET; 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 SHRUT was significantly lower than WKYUT (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 SHRET compared with nontrained SHRUT (78 ± 6 vs. 62 ± 4 ml·kg(-1)·min(-1), respectively; P < 0.05) and restored the magnitude of functional sympatholysis in SHRET (1 Hz: 9 ± 2%; 2.5 Hz: 20 ± 4%; and 5 Hz: 34 ± 5%). Blockade of NO synthase (NOS) by N(G)-nitro-l-arginine methyl ester attenuated functional sympatholysis in WKYUT but not SHRUT. Furthermore, NOS inhibition significantly diminished the improvements in functional sympatholysis in SHRET. These data demonstrate that impairments in functional sympatholysis are normalized via a NO mechanism by voluntary wheel running in hypertensive rats.

Keywords: blood flow; blood pressure; muscle contraction; vascular conductance; voluntary running.

Copyright © 2014 the American Physiological Society.

Figures

Fig. 1.

Original tracings demonstrating the mean arterial pressure (MAP), femoral blood flow (FBF), femoral vascular conductance (FVC), and percent change of FVC responses to lumbar nerve stimulation at 5 Hz during rest (black line) and muscle contraction (grey line) in untrained normotensive Wistar-Kyoto rats (WKYUT), untrained spontaneously hypertensive rats (SHRUT), and exercise-trained SHR (SHRET). Insets: SHRUT and SHRET expand the ordinate so that the FBF and FVC responses to lumbar nerve stimulation can be seen clearly.

Fig. 2.

FBF (A) and FVC (B) responses to lumbar sympathetic nerve stimulation (1, 2.5, and 5 Hz) at rest (solid bars) and during muscle contraction (hatched bars) in WKYUT, SHRUT, and SHRET. *P < 0.05, compared with WKYUT. †P < 0.05, compared with SHRUT.

Fig. 3.

Magnitude of functional sympatholysis calculated as the difference between the percent change in FBF (A) and FVC (B) in response to lumbar nerve stimulation (1, 2.5, and 5 Hz) at rest and during muscle contraction in WKYUT (white bars), SHRUT (black bars), and SHRET (grey bars). *P < 0.05, compared with WKYUT. †P < 0.05, compared with SHRUT.

Fig. 4.

Effect of NG-nitro-l-arginine methyl ester (l-NAME) administration on the magnitude of functional sympatholysis calculated as the difference between the percent change in FBF (A) and FVC (B) in response to lumbar nerve stimulation (5 Hz) at rest and during muscle contraction in WKYUT (white bars), SHRUT (black bars), and SHRET (grey bars) before (solid bars) and after l-NAME administration (hatched bars). §P < 0.05, compared with before l-NAME administration.