title: Azelnidipine decreases sympathetic nerve activity via antioxidant effect in the rostral ventrolateral medulla of stroke-prone spontaneously hypertensive rats.
abstract: The long-acting dihydropyridine calcium channel blocker, azelnidipine, is suggested to inhibit sympathetic nerve activity. We previously demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM) activates sympathetic nerve activity. The aim of the present study was to determine whether oral administration of azelnidipine inhibits sympathetic nerve activity and if so to determine whether the effect is mediated by antioxidant effect in the RVLM. Azelnidipine, hydralazine, or vehicle was orally administered for 28 days to stroke-prone spontaneously hypertensive rats. Reductions in systolic blood pressure were similar in azelnidipine and hydralazine groups. Heart rate was significantly higher in the hydralazine group than in the control, but not altered in the azelnidipine group. Urinary norepinephrine excretion as an indicator of sympathetic nerve activity was significantly lower in the azelnidipine group, whereas it was significantly higher in the hydralazine group than in the control. Levels of thiobarbituric acid-reactive substances and nicotinamide adenine dinucleotide phosphate oxidase activity were significantly lower in the azelnidipine group than in control. Superoxide dismutase activity was significantly increased in the azelnidipine group more than in the control. These results suggest that azelnidipine decreases an indicator of sympathetic nerve activity by antioxidant effect mediated through inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity and activation of superoxide dismutase in the RVLM of stroke-prone spontaneously hypertensive rats.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Konno
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Araki
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Koga
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009638:Norepinephrine / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017392:Thiobarbituric Acid Reactive Substances; D006830:Hydralazine; D001383:Azetidinecarboxylic Acid; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; C061679:azelnidipine; D009638:Norepinephrine