Hypochlorous acid-induced responses in sheep isolated pulmonary artery rings

The formation of reactive oxygen species (ROS) appears to play a significan t role in many pathological states including cystic fibrosis and asthma. Al though stimulated inflammatory cells represent a major source of oxygen met abolites and these cells are able to generate the potent oxidant hypochloro us acid (HOCl) effects of HOCl on arteries are not known. HOCl at low conce ntrations (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 concentr ation reduced histamine-induced relaxations in endothelium intact preparati ons. However, at high concentrations (10(-2) to 1 M) HOCl led to constricti on under resting conditions and caused vasodilation in endothelium intact a nd denuded serotonin (10 mu M) precontracted arteries. These effects of HOC l were significantly reduced by pretreatment of L-arginine (10(-3) M), sodi um nitroprusside (SNP, 10(-5) M) and N-acetyl-L-cysteine (NAC, 10(-4) M). T he effects of SNP and NAC on HOCl-induced responses were due to direct inte raction since only these compounds markedly diminished the HOCl-induced lum inol chemiluminescence (CL). Lack of contraction with KCI after high concen trations 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 inte ract with endothelium-derived mediators and contribute to tissue injury and vascular dysfunction seen in disease states. (C) 2000 Academic Press.