title: Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction.
abstract: Reduced nitric oxide (NO) in the brain might contribute to enhanced sympathetic drive in heart failure (HF). The aim of this study was to determine whether increased NO production induced by local overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarius (NTS) of the brain stem reduces the enhanced sympathetic drive in mice with HF. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. MI mice exhibited left ventricular dilatation and a reduced left ventricular ejection fraction. Urinary norepinephrine excretion in MI mice was greater than that in sham-operated mice, indicating that sympathetic drive was enhanced in this model. Thus this model has features that are typical of HF. Western blot analysis and immunohistochemical staining for neuronal NOS (nNOS) indicated that nNOS protein expression was significantly reduced in the brain stem of MI mice. MI mice had a significantly smaller increase in blood pressure evoked by intracisternal injection of N(G)-monomethyl-L-arginine than sham-operated mice. Adenoviral vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbeta gal) were transfected into the NTS to examine the effect of increased NO production in the NTS on the enhanced sympathetic drive in HF. After the gene transfer, urinary norepinephrine excretion was reduced in AdeNOS-transfected MI mice but not in Adbeta gal-transfected MI mice. These results indicate that nNOS expression in the brain stem, especially in the NTS, is reduced in the MI mouse model of HF, and increased NO production induced by overexpression of eNOS in the NTS attenuates the enhanced sympathetic drive in this model.
authors: Dept. of Cardiovascular Medicine, Kyushu Univ. Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Koji
authors: K
authors: Sakai
authors: Yoshitaka
authors: Y
authors: Hirooka
authors: Hideaki
authors: H
authors: Shigematsu
authors: Takuya
authors: T
authors: Kishi
authors: Koji
authors: K
authors: Ito
authors: Hiroaki
authors: H
authors: Shimokawa
authors: Akira
authors: A
authors: Takeshita
authors: Kenji
authors: K
authors: Sunagawa
mesh_terms: D000256:Adenoviridae / Q000201:enzymology / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D001933:Brain Stem / Q000201:enzymology*; D003331:Coronary Vessels / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D018014:Gene Transfer Techniques; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000201:enzymology* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D009638:Norepinephrine / Q000652:urine; D017552:Solitary Nucleus / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001616:beta-Galactosidase; D009638:Norepinephrine