Inhibition of nitric oxide synthase unmasks vigorous vasoconstriction in established pulmonary arterial hypertension

• Material Type: 博士論文
• Title: Inhibition of nitric oxide synthase unmasks vigorous vasoconstriction in established pulmonary arterial hypertension
• Author/Editor: 石川, 真理子
• Author Heading: 石川, 真理子
• Publication Date: 2018-03-20
• Publication Date (W3CDTF): 2018-03-20
• Alternative Title: 重症肺動脈性肺高血圧症において、一酸化窒素合成酵素の阻害は強い血管過収縮を誘発する
• Contributor: 北園, 孝成; 中西, 洋一; 笹栗, 俊之
• Degree grantor/type: 九州大学
• Date Granted: 2018-03-20
• Date Granted (W3CDTF): 2018-03-20
• Dissertation Number: 甲第13942号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第13942号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): It is widely accepted that impaired bioavailability of endothelial nitric oxide (NO) plays a critical role in the pathophysiology of pulmonary arterial hypertension (PAH). However, there are published data that show that relatively many PAH patients respond favorably to acetylcholine-induced pulmonary vasodilation during their follow-up period, when diverse stages of the disorder are included. We hypothesized that NO bioavailability varies depending on the progression of PAH. Adult rats were exposed to the VEGF receptor blocker Sugen5416 and 3 weeks of hypoxia followed by return to normoxia for various additional weeks. All rats developed increased right ventricular systolic pressure (RVSP) and occlusive lesion formation at 1, 3, 5, and 8 weeks after the Sugen5416 injection. Acute NO synthase blockade did not change the elevated RVSP at the 1-week time point, while it further increased RVSP markedly at the 3-, 5-, and 8-week time points, leading to death in all rats tested at 8 weeks. Acetylcholine caused significant reduction in RVSP at the 8-week but not the 1-week time point, whereas sodium nitroprusside decreased the pressure similarly at both time points. Increased NO-mediated cGMP production was found in lungs from the 8-week but not the 1-week time point. In conclusion, despite its initial impairment, NO bioavailability is restored and endogenous NO plays a critical protective role by counteracting severe pulmonary vasoconstriction in established stages of PAH in the Sugen5416/hypoxia/ normoxia-exposed rats. Our results provide solid pharmacological evidence for a major contribution of a NO-suppressed vasoconstrictor component in the pathophysiology of established PAH.; PubMed番号 : 29208691
• DOI: 10.15017/1931795; https://doi.org/10.15017/1931795
• Persistent ID (NDL): info:ndljp/pid/11122678; https://dl.ndl.go.jp/pid/11122678
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-08-03T23:36:01+09:00
• Date Created (W3CDTF): 2018-05-30
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://dx.doi.org/10.15017/1931795; http://hdl.handle.net/2324/1931795
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

• Summary, etc.: It is widely accepted that impaired bioavailability of endothelial nitric oxide (NO) plays a critical role in the pathophysiology of pulmonary arteria...

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