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[Angiotensin receptor in the lung]
1Department of Internal Medicine of Medical School of Fukuoka University.
Nihon Rinsho. Japanese Journal of Clinical Medicine
|June 11, 1999
Summary
Angiotensin receptor type 1 (AT1) antagonists show promise for treating pulmonary hypertension by improving vessel remodeling. However, effectiveness varies across different PH models, suggesting a complex role for AT1 and AT2 receptors.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Pharmacology
Context:
- Pulmonary hypertension (PH) involves complex vascular remodeling.
- Angiotensin receptors, particularly type 1 (AT1), play a role in pulmonary vasoconstriction.
- Current treatments for PH have limitations, necessitating exploration of novel therapeutic targets.
Purpose:
- To investigate the expression and role of angiotensin receptor subtypes in the lung.
- To evaluate the efficacy of an AT1 antagonist in preclinical models of pulmonary hypertension.
Summary:
- In situ hybridization and ligand-binding assays identified angiotensin receptor type 1 (AT1) as the predominant subtype in pulmonary vessels, with type 2 (AT2) undetectable.
- AT1 receptor activation mediates pulmonary artery contraction via the inositol phosphate-protein kinase C pathway.
- Administration of a non-peptide AT1 antagonist ameliorated pulmonary arterial remodeling and right ventricular hypertrophy in a rat model of hypoxia-induced PH.
- The AT1 antagonist showed limited efficacy in a rat model of monocrotaline-induced PH, potentially due to insufficient AT2 receptor stimulation or differential tissue responses.
Impact:
- This study highlights the differential efficacy of AT1 antagonists in various PH models.
- Findings suggest that targeting the renin-angiotensin system, potentially in combination with other pathways, could be a therapeutic strategy for specific forms of pulmonary hypertension.
- Further research is warranted to elucidate the role of AT2 receptors and optimize therapeutic interventions for PH.