title: Regulation of arterial blood pressure by Akt1-dependent vascular relaxation.
abstract: Endothelial cell-dependent vascular relaxation plays an important role in the regulation of blood pressure. Here, we show that stimulation of vascular endothelial cells with platelet-derived growth factor (PDGF) results in vascular relaxation through Akt1-dependent activation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Stimulation of both human umbilical artery endothelial cells and abdominal aortic vessels with PDGF induced NO production. PDGF-dependent production of NO was completely abolished by inhibition of phosphatidylinositol 3-kinase with wortmannin (100 nM). Stimulation of aortic vessels with PDGF resulted in the activation of Akt phosphorylation and eNOS phosphorylation: however, eNOS phosphorylation and production of NO were abolished in aortic vessels of mice lacking Akt1. PDGF strongly induced vascular relaxation in the presence of endothelium, and inhibition of NO production by N-nitro-L: -arginine-methyl ester completely blocked PDGF-dependent vascular relaxation. In addition, PDGF-dependent relaxation was completely abolished by inhibition of PI3K with wortmannin (100 nM). Furthermore, vessels from Akt1 heterozygotes showed normal relaxation after PDGF stimulation, whereas vessels from Akt1 knockout littermates did not respond to PDGF stimulation. Finally, administration of PDGF (5 ng/ml) significantly lowered blood pressure in Akt1 heterozygotes, whereas a blood pressure-lowering effect was not observed in Akt1 knockout littermates. These results suggest that Akt1 regulates blood pressure through regulation of vascular relaxation by eNOS phosphorylation and subsequent production of NO.
authors.affiliation: MRC for Ischemic Tissue Regeneration and Department of Pharmacology, Pusan National University School of Medicine, Bumeo-ri, Mulgeum-eup, Yangsan-si, Kyungnam, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ha
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.forename: Dong Hyung
authors.initials: DH
authors.lastname: Lee
authors.forename: Sung Ji
authors.initials: SJ
authors.lastname: Yun
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Kim
authors.forename: In
authors.initials: I
authors.lastname: Hye Jin
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
authors.forename: Hwa Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D010982:Platelet-Derived Growth Factor; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt