title: Superoxide Mediates Depressive Effects Induced by Hydrogen Sulfide in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats.
abstract: Hydrogen sulfide (H2S) plays a crucial role in the regulation of blood pressure and oxidative stress. In the present study, we tested the hypothesis that H2S exerts its cardiovascular effects by reducing oxidative stress via inhibition of NADPH oxidase activity in the rostral ventrolateral medulla (RVLM). We examined cell distributions of cystathionine-β-synthase (CBS) and effects of H2S on reactive oxygen species (ROS) and mean arterial blood pressure (MAP) in spontaneously hypertensive rats (SHRs). We found that CBS was expressed in neurons of the RVLM, and the expression was lower in SHRs than in Wistar-Kyoto rats. Microinjection of NaHS (H2S donor), S-adenosyl-l-methionine (SAM, a CBS agonist), or Apocynin (NADPH oxidase inhibitor) into the RVLM reduced the ROS level, NADPH oxidase activity, and MAP, whereas microinjection of hydroxylamine hydrochloride (HA, a CBS inhibitor) increased MAP. Furthermore, intracerebroventricular infusion of NaHS inhibited phosphorylation of p47(phox), a key step of NADPH oxidase activation. Since decreasing ROS level in the RVLM reduces MAP and heart rate and increasing H2S reduces ROS production, we conclude that H2S exerts an antihypertensive effect via suppressing ROS production. H2S, as an antioxidant, may be a potential target for cardiovascular diseases.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China ; Beijing Electric Power Hospital, Capital Medical University, China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China.
authors.forename: Anqi
authors.initials: A
authors.lastname: He
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China ; Department of Medicine, University of Louisville, KY, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Yixueyuan Road 138, Xuhui District, Shanghai 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000737:chemistry / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D019811:Hydroxylamine / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D017382:Reactive Oxygen Species; D013481:Superoxides; D019811:Hydroxylamine; D012436:S-Adenosylmethionine; C056165:acetovanillone; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide