Premium
High blood pressure associates with the remodelling of inward rectifier K + channels in mice mesenteric vascular smooth muscle cells
Author(s) -
Tajada Sendoa,
Cidad Pilar,
MorenoDomínguez Alejandro,
PérezGarcía M. Teresa,
LópezLópez José R.
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.236190
Subject(s) - vascular smooth muscle , inward rectifier potassium ion channel , medicine , mesenteric arteries , bk channel , endocrinology , membrane potential , potassium channel , chemistry , myocyte , vascular remodelling in the embryo , depolarization , vascular tissue , ion channel , microbiology and biotechnology , biology , artery , receptor , biochemistry , smooth muscle , botany
Key points• Essential hypertension involves an electrical remodelling of vascular smooth muscle cells (VSMCs), particularly relevant for K + channels, as key determinants of resting membrane potential ( V M ) and excitability. • We explored mRNA expression levels of inward rectifier K + channel genes in five different vascular beds from normotensive (BPN) and hypertensive (BPH) mice. In mesenteric VSMCs, their functional contribution to cell excitability and vascular reactivity was investigated. • BPH mesenteric VSMCs show a decreased functional expression of both classical inward rectifiers (K IR , Kir2 and Kir4 channels) and ATP‐sensitive K + channels (K ATP , Kir6 channels). However, only the changes in the functional expression of K ATP channels seem to contribute to the increased vascular reactivity of BPH arteries. • BPN and BPH mice are a useful model to provide integrated information of the impact in the pathophysiology of essential hypertension of the changes in ion channel functional expression.Abstract The increased vascular tone that defines essential hypertension is associated with depolarization of vascular smooth muscle cells (VSMCs) and involves a change in the expression profile of ion channels promoting arterial contraction. As a major regulator of VSMC resting membrane potential ( V M ), K + channel activity is an important determinant of vascular tone and vessel diameter. However, hypertension‐associated changes in the expression and/or modulation of K + channels are poorly defined, due to their large molecular diversity and their bed‐specific pattern of expression. Moreover, the impact of these changes on the integrated vessel function and their contribution to the development of altered vascular tone under physiological conditions need to be confirmed. Hypertensive (BPH) and normotensive (BPN) mice strains obtained by phenotypic selection were used to explore whether changes in the functional expression of VSMC inward rectifier K + channels contribute to the more depolarized resting V M and the increased vascular reactivity of hypertensive arteries. We determined the expression levels of inward rectifier K + channel mRNA in several vascular beds from BPN and BPH animals, and their functional contribution to VSMC excitability and vascular tone in mesenteric arteries. We found a decrease in the expression of Kir2.1, Kir4.1, Kir6.x and SUR2 mRNA in BPH VSMCs, and a decreased functional contribution of both K IR and K ATP channels in isolated BPH VSMCs. However, only the effect of K ATP channel modulators was impaired when exploring vascular tone, suggesting that decreased functional expression of K ATP channels may be an important element in the remodelling of VSMCs in essential hypertension.