Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2024-09-09 DOI:10.1111/fcp.13036

Marija Marinko, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He, Aleksandra Novakovic

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Abstract

Background

Changes in K⁺ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K⁺ channels. Their involvement in hydrogen sulfide (H₂S)-mediated vasorelaxation is still unclear, and data about human vessels are limited.

Objective

To determine the role of K⁺ channel subtypes in the vasorelaxant mechanism of H₂S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).

Results

NaHS (1 × 10⁻⁶–3 × 10⁻³ mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K⁺. Among K⁺ channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P < 0.01), whereas in the presence of apamin/1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L-NAME and KT5823, and by cyclo-oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM-34 and glibenclamide caused further decrease in NaHS-induced vasorelaxation (P < 0.01), while iberiotoxin, 4-AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01).

Conclusion

Our results demonstrated that H₂S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H₂S included direct or indirect opening of different K⁺ channel subtypes, K_ATP, BK_Ca, SK_Ca/IK_Ca, and K_V (subtype K_V1.3), in addition to NO pathway activation and interference with extracellular Ca²⁺ influx.

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不同 K+ 通道亚型参与硫化氢诱导的人乳内动脉血管舒张作用

背景：在高血压、糖尿病和动脉粥样硬化等多种病理情况下，K+通道表达/功能的变化与血管反应性的破坏有关。气体递质通过调节离子通道，尤其是 K+ 通道，对机体产生部分影响。它们在硫化氢（H2S）介导的血管舒张中的参与尚不清楚，有关人体血管的数据也很有限：目的：确定 K+ 通道亚型在硫化氢供体钠-硫化氢（NaHS）对离体人乳内动脉（HIMA）的血管舒张机制中的作用：结果：NaHS（1 × 10-6-3 × 10-3 mol/L）可诱导苯肾上腺素和高 K+预收缩的 HIMA 产生浓度依赖性松弛。在 K+ 通道阻滞剂中，依比妥毒素、格列本脲、4-氨基吡啶（4-AP）和玛咖托辛能显著抑制 NaHS 诱导的苯肾上腺素收缩 HIMA 的松弛（P 0.05）。在硝苯地平存在的情况下，NaHS 可诱导 HIMA 部分松弛（P 结论：在硝苯地平存在的情况下，NaHS 可诱导 HIMA 部分松弛：我们的研究结果表明，H2S 供体 NaHS 可诱导离体 HIMA 的浓度依赖性松弛。H2S 的血管舒张机制包括直接或间接打开不同的 K+ 通道亚型：KATP、BKCa、SKCa/IKCa 和 KV（亚型 KV1.3），此外还有 NO 通路激活和干扰细胞外 Ca2+ 流入。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.