Potthoff, Sebastian A. and Quack, Ivo and Mori, Yuri and Yang, Guang and Arifaj, Denada and Amin, Ehsan and Meister, Jaroslawna and Meuth, Sven G. and Kantauskaite, Marta and Argov, Doron and Alesutan, Ioana and Voelkl, Jakob and Park, Joon-Keun and Rump, Lars C. and Rio, Marc and Loirand, Gervaise and Linker, Ralf A. and Stegbauer, Johannes (2025) Role of Ciliary Neurotrophic Factor in Angiotensin II-Induced Hypertension. HYPERTENSION, 82 (4). pp. 652-664. ISSN 0194-911X, 1524-4563
Full text not available from this repository. (Request a copy)Abstract
BACKGROUND:Ciliary neurotrophic factor (CNTF), mainly known for its neuroprotective properties, belongs to the IL-6 (interleukin-6) cytokine family. In contrast to IL-6, the effects of CNTF on the vasculature have not been explored. Here, we examined the role of CNTF in AngII (angiotensin II)-induced hypertension.METHODS:Hypertension was chronically induced with AngII (1000 ng/kg per minute, osmotic mini-pumps, 14 days) in CNTF-knockout and wild-type mice (with or without nephrectomy and 1% NaCl drinking water). Blood pressure was measured by tail-cuff and radiotelemetry. Effects of CNTF on vascular function and the JAK2/STAT3 pathway were measured in vivo, in the isolated perfused kidney, and in mouse and human vascular smooth muscle cells.RESULTS:At baseline, systolic blood pressure was similar between both groups. During AngII infusion, blood pressure increase was significantly attenuated and hypertensive heart and kidney damage was significantly attenuated in CNTF-knockout compared with wild-type mice. Accordingly, renal pressor response to AngII but not KCl or phenylephrine was significantly decreased in CNTF-knockout compared with wild-type mice. Acute CNTF (5 mu mol/L) administration nearly restored the AngII-dependent renal pressor response. Chronic CNTF treatment in CNTF-knockout mice increased blood pressure response to AngII to levels observed in wild-type mice. CNTF augments AngII-induced activation of the JAK2/STAT3 pathway in vitro in vascular smooth muscle cells. The significance of this interaction was shown, as the increase in renal pressor response by CNTF was abolished by JAK2/STAT3 inhibitors.CONCLUSIONS:Our results demonstrate a major impact of CNTF on blood pressure regulation by modulating AngII-induced pressor response via a JAK2/STAT3-dependent mechanism and indicate that CNTF is an important regulatory cytokine in hypertension.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC KIDNEY-DISEASE; BLOOD-PRESSURE; FACTOR CNTF; CARDIAC-HYPERTROPHY; NERVE REGENERATION; INTERLEUKIN-6; RECEPTORS; STAT3; INFLAMMATION; TRANSDUCER; angiotensin II; ciliary neurotrophic factor; hypertension; hypertensive organ damage; interleukin-6; vascular function |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2026 11:41 |
| Last Modified: | 31 Mar 2026 11:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67821 |
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