HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/L559    most recent 00312.2003v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Olson, S. Articles by Burke-Wolin, T. Search for Related Content PubMed PubMed Citation Articles by Olson, S. Articles by Burke-Wolin, T.

Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor

Departments of ¹Biochemistry and Molecular Biology, ²Pathology, and ³Pharmacology, New York Medical College, Valhalla, New York 10595

Submitted 8 September 2003 ; accepted in final form 12 May 2004

We previously reported that angiotensin II stimulates an increase in nitric oxide production in pulmonary artery endothelial cells. The aims of this study were to determine which receptor subtype mediates the angiotensin II-dependent increase in nitric oxide production and to investigate the roles of the angiotensin type 1 and type 2 receptors in modulating angiotensin II-dependent vasoconstriction in pulmonary arteries. Pulmonary artery endothelial cells express both angiotensin II type 1 and type 2 receptors as assessed by RT-PCR, Western blot analysis, and flow cytometry. Treatment of the endothelial cells with PD-123319, a type 2 receptor antagonist, prevented the angiotensin II-dependent increase in nitric oxide synthase mRNA, protein levels, and nitric oxide production. In contrast, the type 1 receptor antagonist losartan enhanced nitric oxide synthase mRNA levels, protein expression, and nitric oxide production. Pretreatment of the endothelial cells with either PD-123319 or an anti-angiotensin II antibody prevented this losartan enhancement of nitric oxide production. Angiotensin II-dependent enhanced hypoxic contractions in pulmonary arteries were blocked by the type 1 receptor antagonist candesartan; however, PD-123319 enhanced hypoxic contractions in angiotensin II-treated endothelium-intact vessels. These data demonstrate that angiotensin II stimulates an increase in nitric oxide synthase mRNA, protein expression, and nitric oxide production via the type 2 receptor, whereas signaling via the type 1 receptor negatively regulates nitric oxide production in the pulmonary endothelium. This endothelial, type 2 receptor-dependent increase in nitric oxide may serve to counterbalance the angiotensin II-dependent vasoconstriction in smooth muscle cells, ultimately regulating pulmonary vascular tone.

nitric oxide synthase; angiotensin type 2 receptor; pulmonary endothelium

This article has been cited by other articles:

				J. Li, X. Zhao, X. Li, K. M. Lerea, and S. C. Olson Angiotensin II type 2 receptor-dependent increases in nitric oxide synthase expression in the pulmonary endothelium is mediated via a G{alpha}i3/Ras/Raf/MAPK pathway Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2185 - C2196. [Abstract] [Full Text] [PDF]

				J. Zheng, Y. Wen, D.-b. Chen, I. M. Bird, and R. R. Magness Angiotensin II Elevates Nitric Oxide Synthase 3 Expression and Nitric Oxide Production Via a Mitogen-Activated Protein Kinase Cascade in Ovine Fetoplacental Artery Endothelial Cells Biol Reprod, June 1, 2005; 72(6): 1421 - 1428. [Abstract] [Full Text] [PDF]