This Article Full Text Full Text (PDF) All Versions of this Article: 43/4/880    most recent 01.HYP.0000120124.27641.03v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takemura, Y. Articles by Ogihara, T. Search for Related Content PubMed PubMed Citation Articles by Takemura, Y. Articles by Ogihara, T. Related Collections Endothelium/vascular type/nitric oxide Apoptosis

(Hypertension. 2004;43:880.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Fas Signaling Induces Akt Activation and Upregulation of Endothelial Nitric Oxide Synthase Expression

Yukihiro Takemura; Keisuke Fukuo; Osamu Yasuda; Takahito Inoue; Norio Inomata; Toyohiko Yokoi; Hidenobu Kawamoto; Toshimitsu Suhara; Toshio Ogihara

From the Department of Geriatric Medicine (Y.T., O.Y., T.Y., H.K., T.S., T.O.), Osaka University Medical School, Japan; Department of Food Sciences and Nutrition (K.F.), School of Human Environmental Sciences, Mukogawa Women’s University, Nishinomiya, Hyogo, Japan; and Pharmaceutical Research Laboratories (T.I., N.I.), Suntory Institute for Biomedical Research, Mishima-gun, Osaka, Japan

Correspondence to Dr Keisuke Fukuo, Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women’s University, 6-46 Ikebiraki-cho, Nishinomiya, Hyogo, 663-8558, Japan. E-mail fukuo{at}mwu.mukogawa-u.ac.jp

A growing body of evidence has shown that Fas, a death receptor, mediates apoptosis-unrelated biological effects. Here, we report that Fas engagement with Fas ligand induced activation of Akt and upregulation of endothelial nitric oxide synthase expression without induction of apoptosis. In the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin, Fas ligand, however, induced apoptosis instead of upregulation of endothelial nitric oxide synthase expression. In vivo, systolic blood pressure was slightly higher in mutant mice with decreased cell surface Fas expression (lpr mice) compared with wild-type mice. In addition, chronic inhibition of nitric oxide synthesis by N^G-nitro-l-arginine induced a progressive increase in the levels of blood pressure in wild-type mice, whereas no further increase in the levels of blood pressure was observed in lpr mice. Furthermore, acetylcholine caused a lesser endothelium-dependent relaxation of the strips from lpr mice compared with wild-type mice, although the vasoconstrictor potency of phenylephrine was not different between the two groups. These findings indicate that Fas signaling may have a role in the regulation of endothelial function and blood pressure through modulating endothelial nitric oxide synthase expression in the Akt signal-dependent manner.

Key Words: endothelial growth factors • nitric oxide synthase • hypertension

This article has been cited by other articles:

				R. Schnabel, M. G. Larson, J. Dupuis, K. L. Lunetta, I. Lipinska, J. B. Meigs, X. Yin, J. Rong, J. A. Vita, C. Newton-Cheh, et al. Relations of Inflammatory Biomarkers and Common Genetic Variants With Arterial Stiffness and Wave Reflection Hypertension, June 1, 2008; 51(6): 1651 - 1657. [Abstract] [Full Text] [PDF]

				L. A. Smyth and H. J.M. Brady cMet and Fas Receptor Interaction Inhibits Death-Inducing Signaling Complex Formation in Endothelial Cells Hypertension, July 1, 2005; 46(1): 100 - 106. [Abstract] [Full Text] [PDF]