Cardiology

Increased inward rectifier K+ current of coronary artery smooth muscle cells in spontaneously hypertensive rats; partial compensation of the attenuated endothelium-dependent relaxation via Ca2+ -activated K+ channels.

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Increased inward rectifier K+ current of coronary artery smooth muscle cells in spontaneously hypertensive rats; partial compensation of the attenuated endothelium-dependent relaxation via Ca2+ -activated K+ channels.

Clin Exp Pharmacol Physiol. 2019 Aug 24;:

Authors: Kim HJ, Yin MZ, Cho S, Kim SE, Choi SW, Ye SK, Yoo HY, Kim SJ

Abstract
Endothelium-dependent vasorelaxation is partly mediated by small-conductance (SK3) and intermediate-conductance Ca2+ -activated K+ channels (SK4) in the endothelium that results in endothelium-dependent hyperpolarization (EDH). Apart from the electrical propagation through myoendothelial gap junctions, the K+ released from the endothelium facilitates EDH by increasing inward rectifier K+ channel (Kir) conductance in smooth muscle cells. The EDH-dependent relaxation of coronary artery (CA) and Kir current in smooth muscle cells (CASMCs) of hypertensive animals are poorly understood despite the critical role of coronary flow in the hypertrophic heart. In spontaneously hypertensive (SHR) and control (WKY) rats, we found attenuation of the CA relaxation by activators of SK3 and SK4 (NS309 and 1-EBIO) in SHR. In isolated CASMCs, whole-cell patch clamp study revealed larger IK ir in SHR than WKY, whereas the myocytes of skeletal and cerebral arteries showed smaller IK ir in SHR than WKY. While the treatment with IK ir inhibitor (0.1 mM Ba2+ ) alone did not affect the WKY-CA, the SHR-CA showed significant contractile response, suggesting relaxing influence of the higher IK ir in the CASMCs of SHR. Furthermore, the attenuation of NS309-induced relaxation of CA by the combined treatment with 0.1 mM Ba2+ was more prominent in SHR than WKY. Our study firstly shows a distinct increase of IK ir in the CASMCs of SHR, which could partly compensate the attenuated relaxation via endothelial SK3 and SK4. This article is protected by copyright. All rights reserved.

PMID: 31444788 [PubMed – as supplied by publisher]

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