مورد إلكتروني
Pirfenidone Is a Vasodilator:Involvement of KV7 Channels in the Effect on Endothelium-Dependent Vasodilatation in Type-2 Diabetic Mice
| العنوان: | Pirfenidone Is a Vasodilator:Involvement of KV7 Channels in the Effect on Endothelium-Dependent Vasodilatation in Type-2 Diabetic Mice |
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| المصدر: | Beck , L , Pinilla , E , Arcanjo , D D R , Hernanz , R , Prat-Duran , J , Petersen , A G , Köhler , R , Sheykhzade , M , Comerma-Steffensen , S & Simonsen , U 2021 , ' Pirfenidone Is a Vasodilator : Involvement of K V 7 Channels in the Effect on Endothelium-Dependent Vasodilatation in Type-2 Diabetic Mice ' , Frontiers in Pharmacology , vol. 11 , 619152 . |
| بيانات النشر: | 2021 |
| تفاصيل مُضافة: | Beck, Lilliana Pinilla, Estéfano Arcanjo, Daniel Dias Rufino Hernanz, Raquel Prat-Duran, Judit Petersen, Asbjørn Graver Köhler, Ralf Sheykhzade, Majid Comerma-Steffensen, Simon Simonsen, Ulf |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Endothelial cell dysfunction and fibrosis are associated with worsening of the prognosis in patients with cardiovascular disease. Pirfenidone has a direct antifibrotic effect, but vasodilatation may also contribute to the effects of pirfenidone. Therefore, in a first study we investigated the mechanisms involved in the relaxant effect of pirfenidone in rat intrapulmonary arteries and coronary arteries from normal mice. Then in a second study, we investigated whether pirfenidone restores endothelial function in the aorta and mesenteric arteries from diabetic animals. From 16–18-week old normal male C57BL/6 mice and normoglycemic (db/db+), and type 2 diabetic (db/db) male and female mice, arteries were mounted in microvascular isometric myographs for functional studies, and immunoblotting was performed. In rat pulmonary arteries and mouse coronary arteries, pirfenidone induced relaxations, which were inhibited in preparations without endothelium. In mouse coronary arteries, pirfenidone relaxation was inhibited in the presence of a nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine (L-NOARG), a blocker of large-conductance calcium-activated potassium channels (BKCa), iberiotoxin, and a blocker of KV7 channels, XE991. Patch clamp studies in vascular smooth muscle revealed pirfenidone increased iberiotoxin-sensitive current. In the aorta and mesenteric small arteries from diabetic db/db mice relaxations induced by the endothelium-dependent vasodilator, acetylcholine, were markedly reduced compared to db/db + mice. Pirfenidone enhanced the relaxations induced by acetylcholine in the aorta from diabetic male and female db/db mice. An opener of KV7 channels, flupirtine, had the same effect as pirfenidone. XE991 reduced the effect of pirfenidone and flupirtine and further reduced acetylcholine relaxations in the aorta. In the presence of iberiotoxin, pirfenidone still increased acetylcholine relaxation in aorta from db/db |
| مصطلحات الفهرس: | coronary arteries, endothelium, large-conductance calcium-activated K channels, mouse aorta, pirfenidone, pulmonary arteries, type 2 diabetes, voltage-gated KV7 channels, article |
| URL: | |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf English |
| أرقام أخرى: | DAV oai:pure.atira.dk:publications/cb1259b2-f6d0-4453-8989-f9bc95d3b4e1 1322756529 |
| المصدر المساهم: | UNIV OF COPENHAGEN From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1322756529 |
| قاعدة البيانات: | OAIster |
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