Marija Marinko, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He, Aleksandra Novakovic
{"title":"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","authors":"Marija Marinko, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He, Aleksandra Novakovic","doi":"10.1111/fcp.13036","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Changes in K<sup>+</sup> 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<sup>+</sup> channels. Their involvement in hydrogen sulfide (H<sub>2</sub>S)-mediated vasorelaxation is still unclear, and data about human vessels are limited.</p><p><strong>Objective: </strong>To determine the role of K<sup>+</sup> channel subtypes in the vasorelaxant mechanism of H<sub>2</sub>S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).</p><p><strong>Results: </strong>NaHS (1 × 10<sup>-6</sup>-3 × 10<sup>-3</sup> mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K<sup>+</sup>. Among K<sup>+</sup> 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).</p><p><strong>Conclusion: </strong>Our results demonstrated that H<sub>2</sub>S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H<sub>2</sub>S included direct or indirect opening of different K<sup>+</sup> channel subtypes, K<sub>ATP</sub>, BK<sub>Ca</sub>, SK<sub>Ca</sub>/IK<sub>Ca</sub>, and K<sub>V</sub> (subtype K<sub>V</sub>1.3), in addition to NO pathway activation and interference with extracellular Ca<sup>2+</sup> influx.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Involvement of different K<sup>+</sup> channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery.\",\"authors\":\"Marija Marinko, Ivan Stojanovic, Predrag Milojevic, Dragoslav Nenezic, Vladimir Kanjuh, Qin Yang, Guo-Wei He, Aleksandra Novakovic\",\"doi\":\"10.1111/fcp.13036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Changes in K<sup>+</sup> 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<sup>+</sup> channels. Their involvement in hydrogen sulfide (H<sub>2</sub>S)-mediated vasorelaxation is still unclear, and data about human vessels are limited.</p><p><strong>Objective: </strong>To determine the role of K<sup>+</sup> channel subtypes in the vasorelaxant mechanism of H<sub>2</sub>S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).</p><p><strong>Results: </strong>NaHS (1 × 10<sup>-6</sup>-3 × 10<sup>-3</sup> mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K<sup>+</sup>. Among K<sup>+</sup> 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).</p><p><strong>Conclusion: </strong>Our results demonstrated that H<sub>2</sub>S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. 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Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery.
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, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx.
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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
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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.
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