Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries

Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S...

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Veröffentlicht in:British journal of pharmacology 2001-07, Vol.133 (5), p.615-624
Hauptverfasser: López‐López, José Gustavo, Pérez‐Vizcaíno, Francisco, Cogolludo, Angel L, Ibarra, Manuel, Zaragozá‐Arnáez, Francisco, Tamargo, Juan
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container_end_page 624
container_issue 5
container_start_page 615
container_title British journal of pharmacology
container_volume 133
creator López‐López, José Gustavo
Pérez‐Vizcaíno, Francisco
Cogolludo, Angel L
Ibarra, Manuel
Zaragozá‐Arnáez, Francisco
Tamargo, Juan
description Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation. Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide. British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103
doi_str_mv 10.1038/sj.bjp.0704103
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The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation. Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide. 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Drug treatments ; piglet ; pulmonary artery ; Pulmonary Artery - drug effects ; Pulmonary Artery - physiology ; SNAP ; Sodium nitroprusside ; superoxide ; Superoxide Dismutase - pharmacology ; Superoxides - metabolism ; Swine ; Swine, Miniature ; Vasodilation - drug effects ; Vasodilator agents. 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The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation. Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide. British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrochemistry</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nitric Oxide - pharmacology</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Oxidative Stress</subject><subject>Oxyhemoglobins - pharmacology</subject><subject>Penicillamine - analogs &amp; derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>piglet</subject><subject>pulmonary artery</subject><subject>Pulmonary Artery - drug effects</subject><subject>Pulmonary Artery - physiology</subject><subject>SNAP</subject><subject>Sodium nitroprusside</subject><subject>superoxide</subject><subject>Superoxide Dismutase - pharmacology</subject><subject>Superoxides - metabolism</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator agents. 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The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619. NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation. The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP. Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation. Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation. Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide. British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>11429384</pmid><doi>10.1038/sj.bjp.0704103</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection
subjects Animals
Biological and medical sciences
Cardiovascular system
Dose-Response Relationship, Drug
Electrochemistry
Free Radical Scavengers - pharmacology
In Vitro Techniques
Male
Medical sciences
Nitric Oxide - pharmacology
Nitric Oxide Donors - pharmacology
Nitroprusside - pharmacology
Oxidative Stress
Oxyhemoglobins - pharmacology
Penicillamine - analogs & derivatives
Penicillamine - pharmacology
Pharmacology. Drug treatments
piglet
pulmonary artery
Pulmonary Artery - drug effects
Pulmonary Artery - physiology
SNAP
Sodium nitroprusside
superoxide
Superoxide Dismutase - pharmacology
Superoxides - metabolism
Swine
Swine, Miniature
Vasodilation - drug effects
Vasodilator agents. Cerebral vasodilators
title Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries
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