Regulation of arterial blood pressure by Akt1-dependent vascular relaxation.

Jung Min Ha, Young Whan Kim, Dong Hyung Lee, Sung Ji Yun, Eun Kyoung Kim, In Hye Jin, Ji Hyun Kim, Chi Dae Kim, Hwa Kyoung Shin, Sun Sik Bae

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.

Journal of molecular medicine (Berlin, Germany) 2011 Dec

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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 endo thelial 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.

Citation

Jung Min Ha, Young Whan Kim, Dong Hyung Lee, Sung Ji Yun, Eun Kyoung Kim, In Hye Jin, Ji Hyun Kim, Chi Dae Kim, Hwa Kyoung Shin, Sun Sik Bae. Regulation of arterial blood pressure by Akt1-dependent vascular relaxation. Journal of molecular medicine (Berlin, Germany). 2011 Dec;89(12):1253-60