Effects of Thromboxane A2 on Chronic Hypoxic Pulmonary Hypertension in the Rat.

• Saito Masayoshi

  Department of Chest Medicine, School of Medicine, Chiba University

• Tatsumi Koichiro

  Department of Chest Medicine, School of Medicine, Chiba University

• Kasahara Yasunori

  Department of Chest Medicine, School of Medicine, Chiba University

• Sugito Kazutoshi

  Department of Chest Medicine, School of Medicine, Chiba University

• Igari Hidetoshi

  Department of Chest Medicine, School of Medicine, Chiba University

• Tani Toshiaki

  Department of Radiology, School of Medicine, Chiba University

• Kuriyama Takayuki

  Department of Chest Medicine, School of Medicine, Chiba University

Bibliographic Information

Other Title

• トロンボキサンＡ２アナログ（ＳＴＡ２）のラット低酸素性肺高血圧に及ぼす影響

Abstract

Chronic hypoxia (10% O₂ for 2-3 weeks) causes pulmonary hypertension and vascular remodeling in the rat. To study the role of thromboxase A₂ in chronic hypoxic pulmonary hypertension, the hemodynamic effects of intravenous administration of a thromboxane analogue (STA₂) were measured in chronic hypoxic (H) and normoxic (N) Sprague-Dawley rats. During anesthesia baseline pulmonary arterial pressure (PAP) was higher in H rats (34.6±1.0mmHg) than in N rats (18.4±1.2mmHg). Intravenous STA₂ (0.3μg) acutely increased pulmonary artery pressure by 74%±11% (25±4mmHg) in H rats and by 47%±2% (9±1mmHg) in N rats, which indicates that both the absolute and relative acute pulmonary vasoconstriction caused by STA₂ were greater in H rats. The changes in systemic arterial pressure caused by STA₂ were smaller than the changes in pulmonary arterial pressure both in H rats (11%±3%) and in N rats (17%±3%). Lungs were isolated and perfused with saline, and the vasoconstrictive response to 0.05μg of STA₂ in lungs (14.5±2.4mmHg) from H rats was greater than the response to 0.1μg of STA₂ (5.6±1.3mmHg) in lungs from N rats. To examine whether blockade of calcium channels could suppress the vasoconstrictor response to STA₂, the effects of the calcium channel blocker nicardipine hydrochloride on vasoconstriction caused by STA₂ were measured in H and N rats. In vivo, the blockade of calcium channels suppressed the increase in pulmonary artery pressure caused by STA₂. This suppression was greater in H rats (56%±11%) than in N rats (25%±4%). Similar results were obtained with isolated perfused lungs. Blockade of calcium channels suppressed the vasoconstriction caused by STA₂ and this suppression was greater in H rats than in N rats. The finding that thromboxane A₂ induced greater vasoconstriction in H rats than in N rats indicates that thromboxane A₂ may play an important role in pulmonary hypertension, and suggests that blockade thromboxane A₂ may benefit some patients with primary and secondary pulmonary hypertension. Furthermore, the finding that suppression of thromboxane-induced vasoconstriction by blockade of calcium channels was greater in H rats than in N rats indicates that such treatment may also benefit some patients.

Journal

• The Japanese journal of thoracic diseases

  The Japanese journal of thoracic diseases 34 (1), 37-44, 1996

  The Japanese Respiratory Society

Keywords

• Thromboxane A₂
• Pulmonary hypertension
• Hypoxic Pulmonary hypertension
• Ca antagonist

Details

• CRID: 1390282679994808960
• NII Article ID: 130003678884
• NII Article ID: 10008109143
• NII Book ID: AN00187758
• DOI: 10.11389/jjrs1963.34.37
• ISSN: 1883471X
• ISSN: 03011542
• Web Site: https://search.jamas.or.jp/link/ui/1996160441
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed