Hypochlorous acid-induced responses in sheep isolated pulmonary artery rings.
The formation of reactive oxygen species (ROS) appears to play a significant role in many pathological states including cystic fibrosis and asthma. Although stimulated inflammatory cells represent a major source of oxygen metabolites and these cells are able to generate the potent oxidant hypochlorous acid (HOCl) effects of HOCl on arteries are not known. HOCl at low concentrations (10(-7)to 10(-4)m) did not affect the resting force or have an action in precontracted sheep pulmonary arteries. HOCl at 10(-4) m concentration reduced histamine-induced relaxations in endothelium intact preparations. However, at high concentrations (10(-2) to 1 m) HOCl led to constriction under resting conditions and caused vasodilation in endothelium intact and denuded serotonin (10 microm) precontracted arteries. These effects of HOCl were significantly reduced by pretreatment of l -arginine (10(-3)m), sodium nitroprusside (SNP, 10(-5) m) and N -acetyl-l-cysteine (NAC, 10(-4) m). The effects of SNP and NAC on HOCl-induced responses were due to direct interaction since only these compounds markedly diminished the HOCl-induced luminol chemiluminescence (CL). Lack of contraction with KCl after high concentrations of HOCl showed that HOCl causes irreversible tissue damage. These results suggest that HOCl produce vasoconstriction under resting force and cause vasodilation when the pulmonary arteries precontracted. HOCl may interact with endothelium-derived mediators and contribute to tissue injury and vascular dysfunction seen in disease states.
Turan
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Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, Ankara, TR-06330, Turkey.
Demiryürek
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AT
Kanzik
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I
D000818:Animals; D003550:Cystic Fibrosis / Q000209:etiology; D004730:Endothelium, Vascular / Q000502:physiology; D006997:Hypochlorous Acid / Q000633:toxicity*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009569:Nitric Oxide / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects*; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide; D006997:Hypochlorous Acid