title: Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart failure and the therapeutic effects of HMG-CoA reductase inhibitor.
abstract: BACKGROUND
  The vascular NAD(P)H oxidase-derived superoxide anion (O(2)-) plays a crucial role in the pathological progression of hypertension and atherosclerosis, and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects. However, it is unclear whether the vascular NAD(P)H oxidase is involved in the endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA reductase inhibitors (statins) exert their vasoprotective effects in CHF. The present study examined both the involvement of vascular NAD(P)H oxidase in endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic effect of a statin (pitavastatin).
  
  
  RESULTS
  Femoral blood flow (FBF) responses to acetylcholine was significantly impaired in the CHF group, but were improved by pitavastatin. Vascular O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression were significantly elevated in CHF compared with the normal group. The elevated O(2)-production in the CHF group was suppressed by the NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither the gene expression nor the activity of endothelial nitric oxide synthase (eNOS) differed significantly between the normal and CHF groups. However, pitavastatin significantly suppressed O(2)- production, NAD(P)H oxidase activity and Nox4 and p47phox expression and increased eNOS expression and activity compared with the CHF group.
  
  
  CONCLUSIONS
  The activated vascular NAD(P)H oxidase contributes to endothelial dysfunction in CHF, which was partly improved by pitavastatin via its inhibition of NAD(P)H oxidase.
authors.affiliation: Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu 520-2192, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takayama
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Wada
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsutamoto
authors.forename: Masato
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Isono
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001808:Blood Vessels / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005263:Femoral Artery / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin / Q000494:pharmacology; D011804:Quinolines / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D014665:Vasodilator Agents; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D005996:Nitroglycerin; C108475:pitavastatin; D000109:Acetylcholine; D002118:Calcium