title: Secondhand tobacco smoke impairs rabbit pulmonary artery endothelium-dependent relaxation.
abstract: OBJECTIVE
  To determine whether secondhand smoke (SHS) induces pulmonary artery endothelial dysfunction, and whether dietary L-arginine supplementation is preventive.
  
  
  BACKGROUND
  SHS causes coronary and peripheral arterial endothelial dysfunction.
  
  
  METHODS
  The effects of L-arginine supplementation (2.25% solution) and SHS (10 weeks) on pulmonary vascular reactivity were examined in 32 rabbits fed a normal diet. Endothelium-dependent relaxation of precontracted pulmonary artery segments was studied using acetylcholine and calcium ionophore. Endothelium-independent relaxation was studied using nitroglycerin. Endothelial and serum L-arginine levels were measured by chromatography. In eight SHS-exposed and in eight control rats, pulmonary artery nitric oxide synthase (NOS) activity and arginase activity were studied using the titrated arginine to citrulline conversion assay.
  
  
  RESULTS
  SHS reduced maximal acetylcholine-induced (p = 0.04) and calcium ionophore-induced (p = 0.02) relaxation. L-Arginine increased maximal acetylcholine-induced (p = 0.047) vasodilation. SHS and L-arginine did not influence nitroglycerin-induced relaxation. SHS reduced endothelial L-arginine (p = 0.04) but not serum L-arginine. L-Arginine supplementation increased endothelial (p = 0.007) and serum L-arginine (p < 0.0005). Endothelium-dependent relaxation induced by acetylcholine and calcium ionophore varied directly with endothelial (r = 0.67, r = 0.67) and serum L-arginine (r = 0.43, r = 0.45), respectively. SHS reduced constitutive NOS activity (p = 0.03).
  
  
  CONCLUSIONS
  SHS reduces pulmonary artery endothelium-dependent relaxation by decreasing NOS activity and possibly by decreasing endothelial arginine content. L-Arginine supplementation increases serum and endothelial L-arginine stores and prevents SHS-induced endothelial dysfunction. L-Arginine may offset the deleterious effect of SHS on pulmonary arteries by substrate loading of the nitric oxide pathway.
authors.affiliation: Division of CardiologyUniversity of California, San Francisco, San Francisco, CA 94143-0124, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hutchison
authors.forename: R E
authors.initials: RE
authors.lastname: Sievers
authors.forename: B Q
authors.initials: BQ
authors.lastname: Zhu
authors.forename: Y P
authors.initials: YP
authors.lastname: Sun
authors.forename: D J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: W W
authors.initials: WW
authors.lastname: Parmley
authors.forename: K
authors.initials: K
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D019001:Nitric Oxide Synthase / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D014028:Tobacco Smoke Pollution; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase; D005996:Nitroglycerin