Dokument: Impact of bradykinin type 2 receptor overexpression on cardiovascular function in mice
| Titel: | Impact of bradykinin type 2 receptor overexpression on cardiovascular function in mice | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=70369 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250728-101301-6 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Metry, Sara [Autor] Suvorava, Tatsiana [Autor] Fischer, Jens W. [Autor] Dao, Vu Thao-Vi [Autor] Kojda, Georg [Autor] | |||||||
| Dateien: |
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| Stichwörter: | Bradykinin type 2 receptor, Flow-mediated dilation, Bradykinin, Echocardiography, Blood pressure | |||||||
| Beschreibung: | Bradykinin is an endogenous peptide playing an important role in regulation of vascular function and permeability, but cardiovascular effects of endogenous bradykinin remain incompletely understood. We studied whether genetically engineered overexpression of endothelial bradykinin type 2 receptor (B2) alters cardiac and vascular function using mice with endothelial-specific overexpression of B2 (B2tg) and their transgene-negative littermates (B2n). In the aorta, brain-stem and skeletal muscle of B2tg human BDKRB2 were exclusively expressed, and B2-overexpression was evident by a significant upregulation of B2 protein. Endothelium-dependent aortic relaxation and responses to phenylephrine or the nitric oxide (NO) donor measured ex vivo were unaffected by the transgene. In contrast, bradykinin induced constriction in B2n, but i vasorelaxation in B2tg that was sensitive to inhibition of NO-synthase (NOS). In vivo assessment of endothelial function by flow-mediated dilation revealed no changes in B2tg as compared to B2n. Likewise, transthoracic echocardiography showed no effect of B2 overexpression on cardiac function. In contrast, decreased systolic blood pressure and bradycardia were observed in B2tg. The decrease in blood pressure in B2tg remained following inhibition of cyclooxygenase and NOS, but was completely abolished by the selective B2 antagonist icatibant. Thus, endothelial-specific B2-overexpression induced mild hypotension and bradycardia while having no effect on flow-mediated dilation or several cardiac function parameters. These minor effects of endothelial-specific B2 overexpression in healthy mice suggest that alterations of endogenous bradykinin generation may not be associated with derangements of cardiovascular functions, however, the long-term safety of continuous changes of bradykinin in cardiovascular comorbidities deserves further rigorous clinical investigation. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Metry, S., Suvorava, T., Fischer, J. W., Dao, V. T.-V., & Kojda, G. (2025). Impact of bradykinin type 2 receptor overexpression on cardiovascular function in mice. Biochemical Pharmacology, 241, Article 117175. https://doi.org/10.1016/j.bcp.2025.117175 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 28.07.2025 | |||||||
| Dateien geändert am: | 28.07.2025 |
