title: Cytosolic phospholipase A2alpha contributes to blood pressure increases and endothelial dysfunction under chronic NO inhibition.
abstract: OBJECTIVE
  Nitric oxide (NO) is an important modulator of cardiovascular function. In this study, we examined whether cytosolic phospholipase A2α (cPLA2α), an initial enzyme in the arachidonic acid pathway, is involved in blood pressure (BP) elevation in a murine model of chronic NO inhibition.
  
  
  RESULTS
  cPLA2α gene-deficient mice (cPLA2α-/-) and wild-type mice (WT) were administered the NO synthesis inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) for 4 weeks. Before treatment, BP was comparable in both groups; it increased significantly in the WT but not in the cPLA2α-/- after treatment. Bone marrow transplantation experiments showed that cPLA2α in blood cells and plasma eicosanoid concentrations were not involved in BP elevation by L-NAME treatment. Activation of cPLA2α and subsequent production of eicosanoids in the aortic endothelium but not in aortic smooth muscle cell, heart, or kidney was observed after L-NAME treatment. Aortic ring assays revealed that endothelial function was comparable in both groups of mice before treatment. L-NAME treatment disturbed endothelial function in WT but not in cPLA2α-/-.
  
  
  CONCLUSIONS
  These results suggest that endothelial cPLA2α may play a principal role in L-NAME-induced hypertension and may be a target molecule for maintaining endothelial function under NO inhibition.
authors.affiliation: Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University Graduate School of Medical Science, and Center for Clinical Residency Program, Tottori University Hospital, 36-1 Nishi-machi, Yonago 683-8504, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ogino
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tsujimoto
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Naonori
authors.initials: N
authors.lastname: Uozumi
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D001794:Blood Pressure; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors; D054513:Group IV Phospholipases A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D012083:Renin / Q000097:blood; D013997:Time Factors; D046509:Tissue Culture Techniques; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015777:Eicosanoids; D004791:Enzyme Inhibitors; C516390:Pla2g4a protein, mouse; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D054513:Group IV Phospholipases A2; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester