title: Cardiac sympathetic hyperinnervation in deoxycorticosterone acetate-salt hypertensive rats.
abstract: Sympathetic activities are elevated in the central SNSs (sympathetic nervous systems) of hypertensive animals, but it is not known whether sympathetic innervation is also elevated in the heart. Sympathetic hyper-responsiveness in hypertension may result from oxidative stress. The aim of the present study was to investigate sympathetic hyperinnervation in DOCA (deoxycorticosterone acetate)-salt hypertensive rats with established hypertension. At 4 weeks after the start of DOCA-salt treatment and uninephrectomization, male Wistar rats were randomized into three groups for 8 weeks: vehicle, NAC (N-acetylcysteine) and triple therapy (hydralazine, hydrochlorothiazide and reserpine). DOCA-salt was associated with increased oxidant release. DOCA-salt produced concentric left ventricular hypertrophy and cardiomyocyte hypertrophy. Sympathetic hyperinnervation was observed in DOCA-salt rats, as assessed by myocardial noradrenaline levels, immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and Western blotting and real-time quantitative RT-PCR (reverse transcription-PCR) of NGF (nerve growth factor). Arrhythmic scores during programmed stimulation in DOCA-salt rats were significantly higher than those in the control rats. Triple therapy, despite being effective on BP (blood pressure), offered neither attenuated cardiomyocyte hypertrophy nor anti-arrhythmia. The effects of DOCA-salt treatment on NGF expression, sympathetic hyperinnervation and arrhythmias were attenuated by NAC. Furthermore, the effects of NAC on NGF were abolished by administering BSO (L-buthionine sulfoximine), an inhibitor of glutamate-cysteine ligase. In conclusion, DOCA-salt treatment contributes to up-regulation of NGF proteins probably through a free radical-dependent pathway in a BP-independent manner. DOCA-salt rats treated with NAC attenuate sympathetic hyperinnervation and thus show a beneficial effect on arrhythmogenic response to programmed electrical stimulation.
authors.affiliation: Cardiology Section, Department of Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Tsung-Ming
authors.initials: TM
authors.lastname: Lee
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
authors.forename: Nen-Chung
authors.initials: NC
authors.lastname: Chang
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D002304:Cardiac Pacing, Artificial; D003900:Desoxycorticosterone / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D008901:Mineralocorticoids; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D013481:Superoxides; D003900:Desoxycorticosterone; D020932:Nerve Growth Factor; D005978:Glutathione; D009638:Norepinephrine