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Vascular smooth muscle contraction in hypertension
#MMPMID29394331
Touyz RM
; Alves-Lopes R
; Rios FJ
; Camargo LL
; Anagnostopoulou A
; Arner A
; Montezano AC
Cardiovasc Res
2018[Mar]; 114
(4
): 529-539
PMID29394331
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Hypertension is a major risk factor for many common chronic diseases, such as
heart failure, myocardial infarction, stroke, vascular dementia, and chronic
kidney disease. Pathophysiological mechanisms contributing to the development of
hypertension include increased vascular resistance, determined in large part by
reduced vascular diameter due to increased vascular contraction and arterial
remodelling. These processes are regulated by complex-interacting systems such as
the renin-angiotensin-aldosterone system, sympathetic nervous system, immune
activation, and oxidative stress, which influence vascular smooth muscle
function. Vascular smooth muscle cells are highly plastic and in pathological
conditions undergo phenotypic changes from a contractile to a proliferative
state. Vascular smooth muscle contraction is triggered by an increase in
intracellular free calcium concentration ([Ca2+]i), promoting actin-myosin
cross-bridge formation. Growing evidence indicates that contraction is also
regulated by calcium-independent mechanisms involving RhoA-Rho kinase, protein
Kinase C and mitogen-activated protein kinase signalling, reactive oxygen
species, and reorganization of the actin cytoskeleton. Activation of
immune/inflammatory pathways and non-coding RNAs are also emerging as important
regulators of vascular function. Vascular smooth muscle cell [Ca2+]i not only
determines the contractile state but also influences activity of many
calcium-dependent transcription factors and proteins thereby impacting the
cellular phenotype and function. Perturbations in vascular smooth muscle cell
signalling and altered function influence vascular reactivity and tone, important
determinants of vascular resistance and blood pressure. Here, we discuss
mechanisms regulating vascular reactivity and contraction in physiological and
pathophysiological conditions and highlight some new advances in the field,
focusing specifically on hypertension.
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