دورية أكاديمية
Eukaryotic elongation factor 2 kinase inhibitor, A484954 induced diuresis via nitric oxide production in spontaneously hypertensive rats.
| العنوان: | Eukaryotic elongation factor 2 kinase inhibitor, A484954 induced diuresis via nitric oxide production in spontaneously hypertensive rats. |
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| المؤلفون: | Kodama T; Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori, Japan., Otani K; Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori, Japan., Okada M; Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori, Japan., Yamawaki H; Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori, Japan. |
| المصدر: | The Journal of veterinary medical science [J Vet Med Sci] 2023 Dec 19; Vol. 85 (12), pp. 1314-1318. Date of Electronic Publication: 2023 Oct 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Japanese Society Of Veterinary Science Country of Publication: Japan NLM ID: 9105360 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1347-7439 (Electronic) Linking ISSN: 09167250 NLM ISO Abbreviation: J Vet Med Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Tokyo : Japanese Society Of Veterinary Science |
| مواضيع طبية MeSH: | Elongation Factor 2 Kinase*/antagonists & inhibitors , Nitric Oxide*, Animals ; Rats ; Blood Pressure ; Diuresis ; Diuretics/pharmacology ; Enzyme Inhibitors/pharmacology ; NF-E2-Related Factor 2/metabolism ; Pyrimidines/pharmacology ; Rats, Inbred SHR |
| مستخلص: | Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a protein kinase that inactivates eEF2, a protein that mediates a peptidyl-tRNA translocation during an elongation step of protein synthesis. We have previously shown that eEF2K was involved in pathogenesis of essential and pulmonary hypertension. A484954 (7-amino-1-cyclopropyl-3-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-6-carboxamide), a selective eEF2K inhibitor, is a membrane permeable small molecule. We have previously shown that A484954 lowered blood pressure and induced diuretic effects in spontaneously hypertensive rats (SHR) due to an increase in renal blood flow. Here we aimed to reveal mechanisms underlying the diuretic effects of A484954 in SHR. A484954-induced diuresis and increase in urinary Na + excretion were inhibited by N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor. A484954 increased mRNA expression of angiotensin type 2 receptor (AT2R) and nuclear factor-erythroid 2-related factor 2 (Nrf2). In summary, we for the first time revealed that A484954 induces diuresis in SHR at least partly via the activation of NO/Nrf2/AT2R pathway. |
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| فهرسة مساهمة: | Keywords: A484954; diuretic effect; eukaryotic elongation factor 2 kinase; nitric oxide |
| المشرفين على المادة: | 0 (A-484954) 0 (Diuretics) EC 2.7.11.20 (Elongation Factor 2 Kinase) 0 (Enzyme Inhibitors) 0 (NF-E2-Related Factor 2) 31C4KY9ESH (Nitric Oxide) 0 (Pyrimidines) |
| تواريخ الأحداث: | Date Created: 20231019 Date Completed: 20240105 Latest Revision: 20240319 |
| رمز التحديث: | 20240319 |
| مُعرف محوري في PubMed: | PMC10788169 |
| DOI: | 10.1292/jvms.23-0306 |
| PMID: | 37853639 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1347-7439 |
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| DOI: | 10.1292/jvms.23-0306 |