Open Access

CFTR deficiency aggravates Ang II induced vasoconstriction and hypertension by regulating Ca2+influx and RhoA/Rock pathway in VSMCs

Liyan Zhao1,2,†,Feng Yuan2,†,Ni Pan2,Yun Yu3,Hanyan Yang2,Yaosheng Liu2,Ruomei Wang4,Bin Zhang5,*, Guanlei Wang2,*
Department of Pharmacy, the First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong, China
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 510080 Guangzhou, Guangdong, China
Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, Guangdong, China
School of Data and Computer Science, Sun Yat-sen University, 51006 Guangzhou, Guangdong, China
Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China
DOI: 10.52586/5034 Volume 26 Issue 12, pp.1396-1410
Submited: 28 September 2021 Revised: 04 November 2021
Accepted: 09 November 2021 Published: 30 December 2021
*Corresponding Author(s):  
Bin Zhang
*Corresponding Author(s):  
Guanlei Wang
These authors contributed equally.
Copyright: © 2021 The author(s). Published by BRI. This is an open access article under the CC BY 4.0 license (

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) has been associated with vascular tone and blood pressure (BP), however, its role in the genesis of hypertension remains elusive. In the present study, we investigated the regulating effect of CFTR on angiotensin II (Ang II) -induced hypertension and defined the molecular role of CFTR in vasoconstriction. Results: We found that CFTR mRNA and protein expression were markedly down-regulated in the arteries from Ang II induced hypertensive animals. During the development of hypertension, BP of Cftr−/−-/- mice was significantly higher than that of Cftr+/++/+ mice. Arteries from Cftr−/−-/- mice or pre-incubated with CFTR specific inhibitor CFTR(inh)-172 exhibited a greater contractile response to Ang II. In vascular smooth muscle cells (VSMCs), the phosphorylation of myosin light chain (MLC), which is the core of VSMCs contraction, was negatively modulated by CFTR. Furthermore, intracellular Ca2+2+ concentration ([Ca2+2+]ii) rise in response to Ang II was negatively modulated by CFTR, while no alteration was observed in resting VSMCs. Ras homolog family member A/Rho-associated protein kinase (RhoA/Rock) mediated phosphorylation of myosin phosphatase target subunit 1 (MYPT1), a regulator of MLC phosphorylation, was negatively modulated by CFTR in both resting and Ang II-stimulated VSMCs. Conclusions: This study demonstrates that CFTR is a negative regulator of vasoconstriction and hypertension, and the underlying mechanism contains two possible pathways: (1) in resting VSMCs, CFTR altered MLC phosphorylation through RhoA/Rock pathway; (2) in Ang II stimulated VSMCs, the regulating effect was mediated by both Ca2+2+ influx and RhoA/Rock mediated pathway.


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Liyan Zhao, Feng Yuan, Ni Pan, Yun Yu, Hanyan Yang, Yaosheng Liu, Ruomei Wang, Bin Zhang, Guanlei Wang. CFTR deficiency aggravates Ang II induced vasoconstriction and hypertension by regulating Ca2+influx and RhoA/Rock pathway in VSMCs. Frontiers in Bioscience-Landmark. 2021. 26(12); 1396-1410.