Regulation of arterial blood pressure by Akt1-dependent vascular relaxation

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 89; no. 12; pp. 1253 - 1260
• Main Authors: Ha, Jung Min, Kim, Young Whan, Lee, Dong Hyung, Yun, Sung Ji, Kim, Eun Kyoung, Hye Jin, In, Kim, Ji Hyun, Kim, Chi Dae, Shin, Hwa Kyoung, Bae, Sun Sik
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2011; Springer; Springer Nature B.V
• Subjects: Animals; Aorta, Abdominal - physiology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood Pressure - physiology; Endothelial Cells - physiology; Endothelium, Vascular - physiology; General aspects; Human Genetics; Human Umbilical Vein Endothelial Cells; Humans; In Vitro Techniques; Internal Medicine; Medical sciences; Mice; Mice, Knockout; Molecular Medicine; Nitric Oxide - physiology; Nitric Oxide Synthase Type III - physiology; Original Article; Platelet-Derived Growth Factor - physiology; Proto-Oncogene Proteins c-akt - physiology; Vasodilation - physiology; Endothelial nitric oxide synthase; Blood pressure; Platelet-derived growth factor; Akt; Vascular relaxation; Angiogenic factor; Enzyme; Akt protein kinase; Nitric-oxide synthase; Medicine; Arterial blood; Relaxation; Regulation(control); Blood vessel; Arterial pressure; Circulatory system; Hemodynamics; Oxidoreductases; Platelet derived growth factor
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-011-0798-3

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.