title: SOD1 gene transfer into paraventricular nucleus attenuates hypertension and sympathetic activity in spontaneously hypertensive rats.
abstract: Excessive sympathetic activity contributes to the initiation and progression of hypertension. Reactive oxygen species in the paraventricular nucleus (PVN) is involved in sympathetic overdrive and hypertension. The present study was designed to investigate whether superoxide dismutase 1 (SOD1) overexpression in the PVN attenuated sympathetic activation and hypertension. Adenoviral vectors containing human SOD1 or null adenoviral vectors were microinjected into the PVN of Wistar rats and spontaneously hypertensive rats (SHR). Significant depressor effects were observed from weeks 1 to 4 after SOD1 gene transfer in SHR. Acute experiments were carried out at the end of the 3rd week. In the PVN, superoxide anion and angiotensin II levels were increased while SOD1 activity and protein expression were decreased in SHR, which were attenuated by SOD1 overexpression in the PVN. However, SOD1 overexpression had no significant effect on the SOD2 activity in the PVN. The blood pressure response to ganglionic blockade, cardiac sympathetic nerve activity, and cardiac sympathetic afferent reflex (CSAR) were enhanced, and the plasma norepinephrine level was increased in SHR, which were prevented by SOD1 gene transfer in the PVN. Furthermore, SOD1 overexpression decreased the ratio of left ventricular weight to body weight, cross-sectional areas of myocardial cells, media thickness, and the media/lumen ratio of small arteries in the heart in SHR. These results indicate that SOD1 overexpression in the PVN reduces arterial blood pressure, attenuates excessive sympathetic activity and CSAR, and improves myocardial and vascular remodeling in SHR.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yuan
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Gao
authors.forename: Ye-Bo
authors.initials: YB
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001158:Arteries / Q000473:pathology; D001794:Blood Pressure; D015870:Gene Expression; D018390:Gene Targeting; D005822:Genetic Vectors; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D015854:Up-Regulation; D000099156:Superoxide Dismutase 2
chemical_list: D000804:Angiotensin II; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D013481:Superoxides; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat