title: 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.
authors.affiliation: Department of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas;
authors.forename: Gary A
authors.initials: GA
authors.lastname: Iwamoto
authors.affiliation: Department of Hypertension Section University of Texas Southwestern Medical Center, Dallas, Texas; and Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Wanpen
authors.initials: W
authors.lastname: Vongpatanasin
authors.affiliation: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Jere H
authors.initials: JH
authors.lastname: Mitchell
authors.affiliation: Department of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, Texas; Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas scott.smith@utsouthwestern.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005081:Exercise Therapy; D005263:Femoral Artery / Q000294:innervation* / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012420:Running; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors; D014661:Vasoconstriction
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: blood flow; blood pressure; muscle contraction; vascular conductance; voluntary running