Prostanoids contribute to regulation of inwardly rectifying K + channels in intrarenal arterial smooth muscle cells.

Aim: The inward rectifier K ⁺ (Kir) channels and prostanoids are important factors in regulating vascular tone, but the relationship between them has not been well studied. We aimed to study the involvement of prostanoids in regulating Kir activity in the rat intrarenal arteries (RIRAs).
Main Methods: The vascular tone of isolated RIRAs was recorded with a wire myograph. The intracellular Ca ²⁺ concentrations ([Ca ²⁺ ] _i ) and Kir currents were measured with a Ca ²⁺ -sensitive fluorescence probe and patch clamp, respectively, in the arterial smooth muscle cell (ASMC) freshly isolated from RIRAs. Kir2.1 expression in RIRAs was assayed by Western blotting.
Key Findings: At 0.03-1.0 mM, BaCl ₂ (a specific Kir blocker) concentration-dependently contracted RIRAs and elevated [Ca ²⁺ ] _i levels. Mild stimulations with various vasoconstrictors at low concentrations significantly potentiated RIRA contraction induced by Kir closure with BaCl ₂ . In both the quiescent and the stimulated RIRAs, cyclooxygenase inhibition and thromboxane-prostanoid receptor (TPR) antagonism depressed BaCl ₂ -induced RIRA contraction, while nitric oxide (NO) synthetase inhibition and endothelium-denudation enhanced the contraction. Kir2.1 expression was significantly more abundant in smaller RIRAs. Ba ²⁺ -sensitive Kir currents were depressed by TPR agonist U46619 while increased by NO donor sodium nitroprusside.
Significance: The present results reveal that vasoconstrictor stimulation augments RIRA contraction induced by Kir closure with Ba ⁺ and indicate that prostanoid synthesis followed by TPR activation is involved in the modulation of the myocyte Kir activity. This study suggests that prostanoid synthesis and TPR may be potential targets for dysfunctions in renal blood circulation.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2020. Published by Elsevier Inc.)