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Perivascular adipose tissue and the dynamic regulation of K v 7 and K ir channels: Implications for resistant hypertension
Author(s) -
Gollasch Maik,
Welsh Donald G.,
Schubert Rudolf
Publication year - 2018
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12434
Subject(s) - inward rectifier potassium ion channel , medicine , vasodilation , adipose tissue , potassium channel , obstructive sleep apnea , diabetes mellitus , vascular smooth muscle , endocrinology , pharmacology , ion channel , receptor , smooth muscle
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 as minoxidil is the only clinically used K + channel opener today, which targets a subclass of K + channels, namely K ATP channels in VSMC s. 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 VSMC s as potential novel drug targets for treatment of resistant hypertension, particularly in comorbid conditions such as obesity and metabolic syndrome.