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Regulation of arterial blood pressure by Akt1-dependent vascular relaxation

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An Erratum to this article was published on 20 March 2013

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.

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Acknowledgments

This work was supported partly by the MRC program of the NRF (2011-0006188) and a National Research Foundation of Korea grant funded by the Korea government (MEST) (2010-0015808).

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Authors and Affiliations

  1. MRC for Ischemic Tissue Regeneration and Department of Pharmacology, Pusan National University School of Medicine, Bumeo-ri, Mulgeum-eup, Yangsan-si, Kyungnam, 626-870, Republic of Korea

    Jung Min Ha, Young Whan Kim, Sung Ji Yun, Eun Kyoung Kim, In Hye Jin, Chi Dae Kim & Sun Sik Bae

  2. Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Bumeo-ri, Mulgeum-eup, Yangsan-si, Kyungnam, 626-870, Republic of Korea

    Dong Hyung Lee

  3. Department of Anatomy, Pusan National University School of Korean Medicine, Bumeo-ri, Mulgeum-eup, Yangsan-si, Kyungnam, 626-870, Republic of Korea

    Ji Hyun Kim & Hwa Kyoung Shin

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  1. Jung Min Ha
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Correspondence to Sun Sik Bae.

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Jung Min Ha and Young Whan Kim contributed equally to this work.

An erratum to this article can be found online at http://dx.doi.org/10.1007/s00109-013-1023-3.

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Ha, J.M., Kim, Y.W., Lee, D.H. et al. Regulation of arterial blood pressure by Akt1-dependent vascular relaxation. J Mol Med 89, 1253–1260 (2011). https://doi.org/10.1007/s00109-011-0798-3

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  • DOI: https://doi.org/10.1007/s00109-011-0798-3

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