Perivascular adipose tissue and the dynamic regulation of K_v7 and K_ir channels: Implications for resistant hypertension

Abstract

potential for potassium ions; EPAC, exchange protein directly activated by cAMP; KCNQ channels, voltage-gated potassium channels encoded by KCNQ genes; K ir channels, inwardly rectifying potassium channels; K v channels, voltage-gated potassium channels; PVAT, perivascular adipose tissue; VSMC, vascular smooth muscle cell; XE991, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride.*Equal contribution as senior authors. AbstractResistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive drugs at adequate doses.

Negative feedback regulation of vasocontraction by potassium channels in 10‐ to 15‐day‐old rats: Dominating role of Kv7 channels

“…The K v 7 channel blocker XE991 at 3 μmol L −1 caused the development of a strong basal tone and a powerful shift of the methoxamine concentration‐response relationship to the left in arteries of 10‐ to 15‐day‐old rats (Figures and B). However, in arteries of 2‐ to 3‐month‐old rats XE991 induced only a slight increase in the contractile responses to methoxamine (Figure A).…”

“…In addition, XE991 strongly increased the contractile responses to the thromboxane A2 receptor agonist U46619 in arteries from 10‐ to 15‐day‐old but was ineffective in arteries from 2‐ to 3‐month‐old rats (Figure ). Another K v 7 channel blocker, linopirdine, at 10 μmol L −1 also caused the development of a strong basal tone and increased the responses to methoxamine in arteries from 10‐ to 15‐day‐old rats, but had no effect in arteries from 2‐ to 3‐month‐old rats (Figure ). Thus, the negative feedback regulation of vasocontraction by K v 7 channels is much stronger in vessels from 10‐ to 15‐day‐old in comparison to 2‐ to 3‐month‐old rats.…”

Drug Repurposing Patent Applications January–March 2020

“…Open KCNQ channels hyperpolarize and stabilize excitable cells such as autonomic neurons and vascular smooth muscle cells; they have been suggested as therapeutics for resistant hypertension, which is frequently associated with sleep apnea. 32,33 It would be interesting to see what a peripherally restricted drug of this type could achieve in sleep apnea.…”

Plasticity of Adipose Tissue-Derived Stem Cells and Regulation of Angiogenesis

“…Perivascular location of ASCs might suggest their contribution to a well-known endocrine and paracrine activity of adipose tissue surrounding medium- and large-sized vessels in the context of the so-called adipose-vascular coupling ( Gollasch and Dubrovska, 2004 ; Gollasch, 2017 ; Gollasch et al, 2018 ). The PVAT is in direct contact with the vessel adventitia, which is considered as a progenitor cell niche within the vessel wall inhabited by a huge number of stem cells and progenitors, i.e., endothelial progenitor cells (EPCs), progenitors for SMCs, mesenchymal stem cells (MSCs), mesangial cells coexpressing both endothelial and myogenic markers, and organ- and tissue-specific progenitors, i.e., neural stem cells in neural tissue ( Ergun et al, 2011 ; Majesky et al, 2011 ).…”