{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T10:12:38Z","timestamp":1750846358826},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,9,23]],"date-time":"2008-09-23T00:00:00Z","timestamp":1222128000000},"content-version":"vor","delay-in-days":3128,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>S\u2010morpholinosydnonimine (SIN\u20101) is thought to generate peroxynitrite. Recent reports suggested that peroxynitrite possessed a potent vascular relaxant activity via guanylate cyclase activation. However, no previous studies have examined the relaxant effect of peroxynitrite on airway smooth muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the mechanism of bronchoprotection by SIN\u20101, considering in particular the involvement of nitric oxide (NO) and peroxynitrite.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peroxynitrite formation was assayed by monitoring the oxidizing activity of dihydrorhodamine 123, and NO was measured polarographically as a redox current <jats:italic>in vitro<\/jats:italic>. We examined the effect of SIN\u20101 delivered to the airway by ultrasonic nebulization against bronchoconstriction induced by acetylcholine in anaesthetized guinea pigs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SIN\u20101 produced peroxynitrite in a time\u2010 and concentration\u2010dependent manner, but did not produce NO <jats:italic>in vitro<\/jats:italic>. However, when mixed with glutathione (GSH) and bronchoalveolar lavage fluid (BALF), peroxynitrite formation by SIN\u20101 was inhibited and SIN\u20101 induced the release of NO. SNAP (S\u2010nitroso\u2010N\u2010acetyl\u2010penicillamine) and SIN\u20101 each inhibited acetylcholine\u2010induced bronchoconstriction in a dose\u2010dependent manner <jats:italic>in vivo<\/jats:italic>. Though GSH alone did not have any effect on baseline airway resistance and acetylcholine\u2010induced bronchoconstriction, pretreatment with GSH significantly enhanced SNAP\u2010 and SIN\u20101\u2010induced bronchoprotection. In addition, pretreatment with carboxy\u2010PTIO, a NO scavenger, completely inhibited bronchoprotective effect of SNAP on acetylcholine\u2010induced bronchoconstriction, but partially inhibited SIN\u20101\u2010induced bronchoprotection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings demonstrated that SIN\u20101 is a potent peroxynitrite\u2010releasing compound and caused significant bronchoprotection against acetylcholine. The mechanism of bronchoprotection by SIN\u20101 appears to be mediated by peroxynitrite but also at least in part through NO regeneration, which may involve GSH and airway thiols as a consequence of exposure to peroxynitrite.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2222.2000.00715.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T09:42:35Z","timestamp":1047375755000},"page":"445-450","source":"Crossref","is-referenced-by-count":6,"title":["Possible mechanism of bronchoprotection by SIN\u20101 in anaesthetized guinea pigs: roles of nitric oxide and peroxynitrite"],"prefix":"10.1111","volume":"30","author":[{"family":"Kanazawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Hirata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,9,23]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1994.tb02721.x"},{"key":"e_1_2_5_3_2","first-page":"154","article-title":"The relaxant properties in guinea pig airways of S\u2010nitrothiols","volume":"261","author":"Jansen A","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115877"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/148.3.727"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1620"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.29.17355"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00413-4"},{"key":"e_1_2_5_9_2","first-page":"1114","article-title":"Peroxynitrite, a product of superoxide and nitric oxide, produces coronary vasorelaxation in dogs","volume":"268","author":"Liu S","year":"1994","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_10_2","first-page":"H2108","article-title":"Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite","volume":"266","author":"Wu M","year":"1994","journal-title":"Am J Phisiol"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)64313-7"},{"key":"e_1_2_5_12_2","first-page":"L397","article-title":"Antioxidant properties of guinea pig tracheal epithelial cells in vitro","volume":"266","author":"Cohn LA","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.341718"},{"key":"e_1_2_5_14_2","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1152\/jappl.1988.65.6.2585","article-title":"Airway neutral endopeptide\u2010like enzyme modulates tachykinin\u2010 induced bronchoconstriction in vivo","volume":"65","author":"Dusser DJ","year":"1988","journal-title":"J Appl Physiol"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1685"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00011a008"},{"key":"e_1_2_5_17_2","first-page":"L9","article-title":"Changes in cytosolic cGMP and calcium in airway smooth muscle relaxed by 3\u2010morpholinosydronimine","volume":"266","author":"Jones KA","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_5_18_2","first-page":"1215","article-title":"Role of soluble guanylyl cyclase in the relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea and human bronchus","volume":"280","author":"Ellis JL","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_19_2","first-page":"L437","article-title":"NO elicits prolonged relaxation of bovine pulmonary arteries via endogenous peroxynitrite generation","volume":"273","author":"Davidson CA","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.3.H1001"},{"key":"e_1_2_5_21_2","first-page":"H1038","article-title":"Nitrogen dioxide causes pulmonary arterial relaxation via thiol nitrosation and NO formation","volume":"270","author":"Davidson CA","year":"1996","journal-title":"Am J Physiol"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.274.1.L112"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)70024-1"}],"container-title":["Clinical &amp; 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