IMR Press / FBL / Volume 26 / Issue 12 / DOI: 10.52586/5034
Open Access Original Research
CFTR deficiency aggravates Ang II induced vasoconstriction and hypertension by regulating Ca𝟐+ influx and RhoA/Rock pathway in VSMCs
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1 Department of Pharmacy, the First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong, China
2 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 510080 Guangzhou, Guangdong, China
3 Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120 Guangzhou, Guangdong, China
4 School of Data and Computer Science, Sun Yat-sen University, 51006 Guangzhou, Guangdong, China
5 Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China
*Correspondence: (Guanlei Wang); (Bin Zhang)
These authors contributed equally.
Academic Editor: Graham Pawelec
Front. Biosci. (Landmark Ed) 2021, 26(12), 1396–1410;
Submitted: 28 September 2021 | Revised: 4 November 2021 | Accepted: 9 November 2021 | Published: 30 December 2021
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+ concentration ([Ca2+]i) 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+ influx and RhoA/Rock mediated pathway.

Vascular smooth muscle cells
Fig. 1.
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