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

Susan Olson, Richard Oeckler, Xinmei Li, Litong Du, Frank Traganos, Xiangmin Zhao, Theresa Burke-Wolin

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number3 31-3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Angiotensin II
Pulmonary Artery
Endothelium
Nitric Oxide
Endothelial Cells
Nitric Oxide Synthase
Angiotensin Type 1 Receptor
Losartan
Vasoconstriction
Messenger RNA
Angiotensin II Type 2 Receptor Blockers
Lung
Proteins
Smooth Muscle Myocytes
Blood Vessels
Flow Cytometry
Western Blotting
Polymerase Chain Reaction
Antibodies
PD 123319

Keywords

  • Angiotensin type 2 receptor
  • Nitric oxide synthase
  • Pulmonary endothelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor. / Olson, Susan; Oeckler, Richard; Li, Xinmei; Du, Litong; Traganos, Frank; Zhao, Xiangmin; Burke-Wolin, Theresa.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 287, No. 3 31-3, 09.2004.

Research output: Contribution to journalArticle

Olson, Susan ; Oeckler, Richard ; Li, Xinmei ; Du, Litong ; Traganos, Frank ; Zhao, Xiangmin ; Burke-Wolin, Theresa. / Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2004 ; Vol. 287, No. 3 31-3.
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