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Perivascular adipose tissue and the dynamic regulation of K(V)7 and K(ir) channels: implications to resistant hypertension

Item Type:Review
Title:Perivascular adipose tissue and the dynamic regulation of K(V)7 and K(ir) channels: implications to resistant hypertension
Creators Name:Gollasch, M., Welsh, D.G. and Schubert, R.
Abstract:Resistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive drugs at adequate doses. Resistant hypertension is an increasingly common clinical problem in older age, obesity, diabetes, sleep apnea, and chronic kidney disease. Although the direct vasodilator minoxidil was introduced in the early 1970s, only recently has this drug been shown to be particularly effective in a subgroup of patients with treatment-resistant or uncontrolled hypertension. This pharmacological approach is interesting from a mechanistic perspective since minoxidil is the only clinically used K(+) channel opener today, which targets a subclass of K(+) channels, namely K(ATP) channels in vascular smooth muscle cells (VSMCs). Beside K(ATP) channels, two other classes of VSMC K(+) channels could represent novel effective targets for treatment of resistant hypertension, namely K(V)7 (KCNQ) and inward rectifier potassium (K(ir) 2.1) channels. Interestingly, these channels are unique among VSMC potassium channels. First, both have been implicated in the control of microvascular tone by perivascular adipose tissue. Second, they exhibit biophysical properties strongly controlled and regulated by membrane voltage, but not intracellular calcium. This review focuses on K(V)7 (K(V)7.1-5) and K(ir) (K(ir) 2.1) channels in VSMCs as potential novel drug targets for treatment of resistant hypertension, particularly in comorbid conditions such as obesity and metabolic syndrome.
Keywords:Adipocyte-Derived Relaxing Factor, Adipose Tissue, ADRF, KCNQ Channels, K(IR) Channels, Perivascular Relaxing Factors, Animals
Page Range:e12434
Date:January 2018
Official Publication:https://doi.org/10.1111/micc.12434
PubMed:View item in PubMed

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