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09.11.2016 | Original articles

Role of nifedipine and hydrochlorothiazide in MAPK activation and vascular smooth muscle cell proliferation and apoptosis

verfasst von: J. Wang, K. Liu, H. Wang, Z. Li, Y. Li, S. Ping, A. S. A. Bardeesi, Y. Guo, Y. Zhou, T. Pei, L. Deng, P. Sheng, S. Liu, C. Li

Erschienen in: Herz | Ausgabe 6/2017

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Abstract

Background

Once hypertension is established, increased mechanical stretch stress becomes a leading cause of vascular remodeling. Clinical antihypertension guidelines demonstrate that antihypertension drugs prevent vascular remodeling in hypertensive patients mainly by lowering blood pressure, suggesting an indirect way of reducing the effects of stretch stress (hypertension). Whether these drugs can directly block the effects of the stretch stress on vascular remodeling has not been reported to date. This study was designed to answer this question and explore the underlying mechanisms.

Methods

Cultured quiescent vascular smooth muscle cells (VSMCs) were stimulated by stretch stress after pretreatment with nifedipine and hydrochlorothiazide. The phosphorylation levels of extracellular signal-regulated kinases (ERKs), c‑Jun NH₂-terminal protein kinases (JNKs), and p38 mitogen-activated protein kinase (MAPK) in VSMCs were detected via Western blotting. The treated cells were stained using triple-labeled immunofluorescence with Ki67 antibody and a TUNEL kit in the presence of DAPI for the detection of proliferative, apoptotic, and resting cells.

Results

Compared with the negative control, both nifedipine and hydrochlorothiazide had no influence on the phosphorylation of MAPKs and on the proliferation and apoptosis of VSMCs in resting state. Stretch stress could significantly induce increased phosphorylation of MAPKs as well as proliferation and apoptosis of VSMCs. Nifedipine inhibited the effects of stretch stress in a dose-dependent manner. Contrary to the effects of nifedipine, hydrochlorothiazide synergistically amplified the effects induced by stretch stress.

Conclusion

Nifedipine and hydrochlorothiazide have opposing functions in the increased phosphorylation of MAPK and in the proliferation and apoptosis of VSMCs induced by stretch stress. The former plays a role as an inhibitor, while the latter functions as a promoter.

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Titel: Role of nifedipine and hydrochlorothiazide in MAPK activation and vascular smooth muscle cell proliferation and apoptosis
verfasst von: J. Wang
K. Liu
H. Wang
Z. Li
Y. Li
S. Ping
A. S. A. Bardeesi
Y. Guo
Y. Zhou
T. Pei
L. Deng
P. Sheng
S. Liu
C. Li
Publikationsdatum: 09.11.2016
Verlag: Springer Medizin
Erschienen in: Herz / Ausgabe 6/2017
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI: https://doi.org/10.1007/s00059-016-4489-2

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Abstract

Background

Methods

Results

Conclusion

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