title: Sympathoinhibition induced by centrally administered atorvastatin is associated with alteration of NAD(P)H and Mn superoxide dismutase activity in rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats.
abstract: Oxidative stress in the rostral ventrolateral medulla (RVLM) increases sympathetic nervous system activity (SNA). Oral treatment with atorvastatin decreases SNA through antioxidant effects in the RVLM of stroke-prone spontaneously hypertensive rats (SHRSP). We aimed to examine whether centrally administered atorvastain reduces SNA in SHRSP and, if so, to determine whether it is associated with the reduction of oxidative stress induced by alteration of activities of nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase and superoxide dismutase (SOD) in the RVLM of SHRSP. SHRSP received atorvastatin (S-ATOR) or vehicle (S-VEH) by continuous intracerebroventricular infusion for 14 days. Mean blood pressure, heart rate, and SNA were significantly lower in S-ATOR than in S-VEH. Oxidative stress, Rac1 activity, NAD(P)H oxidase activity, Rac1, gp91(phox) and p22(phox) expression in the membrane fraction, and p47(phox) and p40(phox) expression in the cytosolic fraction in the RVLM were significantly lower in S-ATOR than in S-VEH. Rac1 expression in the cytosolic fraction and Mn-SOD activity, however, were significantly higher in S-ATOR than in S-VEH. Our findings suggest that centrally administered atorvastatin decreases SNA and is associated with decreasing NAD(P)H oxidase activity and upregulation of Mn-SOD activity in the RVLM of SHRSP, leading to suppressing oxidative stress.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Satomi
authors.initials: S
authors.lastname: Konno
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology*; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000188:drug therapy / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000201:enzymology
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D009249:NADP; D000069059:Atorvastatin; D013482:Superoxide Dismutase