Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Apr;81(4):752-763.
doi: 10.1161/HYPERTENSIONAHA.123.19434. Epub 2024 Jan 4.

Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels

Fred S Lamb  1 , Hyehun Choi  1 , Michael R Miller  1 , Ryan J Stark  1
Affiliations
Review

Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels

Fred S Lamb et al. Hypertension. 2024 Apr.

Abstract

Vascular inflammation underlies the development of hypertension, and the mechanisms by which it increases blood pressure remain the topic of intense investigation. Proinflammatory factors including glucose, salt, vasoconstrictors, cytokines, wall stress, and growth factors enhance contractility and impair relaxation of vascular smooth muscle cells. These pathways share a dependence upon redox signaling, and excessive activation promotes oxidative stress that promotes vascular aging. Vascular smooth muscle cell phenotypic switching and migration into the intima contribute to atherosclerosis, while hypercontractility increases systemic vascular resistance and vasospasm that can trigger ischemia. Here, we review factors that drive the initiation and progression of this vasculopathy in vascular smooth muscle cells. Emphasis is placed on the contribution of reactive oxygen species generated by the Nox1 NADPH oxidase which produces extracellular superoxide (O2•-). The mechanisms of O2•- signaling remain poorly defined, but recent evidence demonstrates physical association of Nox1 with leucine-rich repeat containing 8 family volume-sensitive anion channels. These may provide a pathway for influx of O2•- to the cytoplasm, creating an oxidized cytoplasmic nanodomain where redox-based signals can affect both cytoskeletal structure and vasomotor function. Understanding the mechanistic links between inflammation, O2•- and vascular smooth muscle cell contractility may facilitate targeting of anti-inflammatory therapy in hypertension.

Keywords: NADPH oxidases; blood pressure; blood vessels; hypertension; inflammation; rho-associated kinases; superoxides.

PubMed Disclaimer

Conflict of interest statement

None.

Similar articles

See all similar articles

Cited by

References

    1. Bohr DF, Dominiczak AF, Webb RC. Pathophysiology of the vasculature in hypertension. Hypertension 1991;18:III69–75. doi: 10.1161/01.hyp.18.5_suppl.iii69 - DOI - PubMed
    1. Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, Montezano AC. Vascular smooth muscle contraction in hypertension. Cardiovasc Res 2018;114:529–539. doi: 10.1093/cvr/cvy023 - DOI - PMC - PubMed
    1. Humphrey JD. Mechanisms of Vascular Remodeling in Hypertension. American journal of hypertension 2021;34:432–441. doi: 10.1093/ajh/hpaa195 - DOI - PMC - PubMed
    1. Falkner B, Gidding SS, Baker-Smith CM, Brady TM, Flynn JT, Malle LM, South AM, Tran AH, Urbina EM, American Heart Association Council on H, et al. Pediatric Primary Hypertension: An Underrecognized Condition: A Scientific Statement From the American Heart Association. Hypertension 2023;80:e101–e111. doi: 10.1161/HYP.0000000000000228 - DOI - PubMed
    1. Luft FC. What Have We Learned from the Genetics of Hypertension? Med Clin North Am 2017;101:195–206. doi: 10.1016/j.mcna.2016.08.015 - DOI - PubMed

MeSH terms