Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor
Autor: | Susan C. Olson, Xinmei Li, Richard A. Oeckler, Frank Traganos, Litong Du, T. Burke-Wolin, Xiangmin Zhao |
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Rok vydání: | 2004 |
Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Angiotensin receptor Nitric Oxide Synthase Type III Endothelium Physiology Pulmonary Artery Nitric Oxide Receptor Angiotensin Type 2 Muscle Smooth Vascular Receptor Angiotensin Type 1 Nitric oxide chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Vasoconstrictor Agents Antihypertensive Agents Cells Cultured Angiotensin II receptor type 1 Dose-Response Relationship Drug biology Angiotensin II Angiotensin-converting enzyme Cell Biology Peptide Fragments Nitric oxide synthase Dithiothreitol Endocrinology Losartan medicine.anatomical_structure chemistry Vasoconstriction biology.protein Cattle Endothelium Vascular Angiotensin I Nitric Oxide Synthase Signal Transduction medicine.drug |
Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 287:L559-L568 |
ISSN: | 1522-1504 1040-0605 |
DOI: | 10.1152/ajplung.00312.2003 |
Popis: | 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. |
Databáze: | OpenAIRE |
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