title: Chronic vagal nerve stimulation prevents high-salt diet-induced endothelial dysfunction and aortic stiffening in stroke-prone spontaneously hypertensive rats.
abstract: Parasympathetic activity is often reduced in hypertension and can elicit anti-inflammatory mechanisms. Thus we hypothesized that chronic vagal nerve stimulation (VNS) may alleviate cardiovascular end-organ damage in stroke-prone spontaneously hypertensive rats. Vagal nerve stimulators were implanted, a high-salt diet initiated, and the stimulators turned on (VNS, n = 10) or left off (sham, n = 14) for 4 wk. Arterial pressure increased equally in both groups. After 4 wk, endothelial function, assessed by in vivo imaging of the long posterior ciliary artery (LPCA) after stimulation (pilocarpine) and inhibition (N(ω)-nitro-l-arginine methyl ester) of endothelial nitric oxide synthase (eNOS), had significantly declined (-2.3 ± 1.2 μm, P < 0.05) in sham, but was maintained (-0.7 ± 0.8 μm, nonsignificant) in VNS. Furthermore, aortic eNOS activation (phosphorylated to total eNOS protein content ratio) was greater in VNS (0.83 ± 0.07) than in sham (0.47 ± 0.08, P < 0.05). After only 3 wk, ultrasound imaging of the aorta demonstrated decreased aortic strain (-9.7 ± 2.2%, P < 0.05) and distensibility (-2.39 ± 0.49 1,000/mmHg, P < 0.05) and increased pulse-wave velocity (+2.4 ± 0.7 m/s, P < 0.05) in sham but not in VNS (-3.8 ± 3.8%, -0.70 ± 1.4 1,000/mmHg, and +0.1 ± 0.7 m/s, all nonsignificant). Interleukin (IL)-6 serum concentrations tended to be higher in VNS than in sham (34.3 ± 8.3 vs. 16.1 ± 4.6 pg/ml, P = 0.06), and positive correlations were found between NO-dependent relaxation of the LPCA and serum levels of IL-6 (r = +0.70, P < 0.05) and IL-10 (r = +0.56, P < 0.05) and between aortic eNOS activation and IL-10 (r = +0.48, P < 0.05). In conclusion, chronic VNS prevents hypertension-induced endothelial dysfunction and aortic stiffening in an animal model of severe hypertension. We speculate that anti-inflammatory mechanisms may contribute to these effects.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa; Veterans Affairs Medical Center, Iowa City, Iowa.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Chapleau
authors.affiliation: Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa;
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rotella
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa; and.
authors.forename: John J
authors.initials: JJ
authors.lastname: Reho
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City, Iowa; and.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.affiliation: Department of Health and Human Physiology, University of Iowa, Iowa City, Iowa; harald-stauss@uiowa.edu.
authors.forename: Harald M
authors.initials: HM
authors.lastname: Stauss
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology*; D062186:Arterial Pressure; D019842:Ciliary Arteries / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004789:Enzyme Activation; D006339:Heart Rate; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D058542:Implantable Neurostimulators; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011918:Rats, Inbred SHR; D012720:Severity of Illness Index; D017673:Sodium Chloride, Dietary; D020521:Stroke / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D055536:Vagus Nerve Stimulation / Q000295:instrumentation / Q000379:methods*; D059289:Vascular Stiffness; D014664:Vasodilation
chemical_list: D015850:Interleukin-6; D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat
keywords: aortic distensibility; aortic pulse-wave velocity; cardiovascular end-organ damage; hypertension; nitric oxide-dependent relaxation