{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:25:37Z","timestamp":1790378737217,"version":"4.1.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>ODQ, (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase) inhibits vasorelaxant responses to nitric oxide (NO)-donor drugs, but the extent of the inhibition varies depending on the NO donor studied. The purpose of this study was to test the hypothesis that these variations in the effects of ODQ reflect differences in the mechanisms whereby each NO donor generates NO.<\/jats:p>\n               <jats:p>On pulmonary artery preparations pre-contracted submaximally with phenylephrine, ODQ (3 \u03bcM) almost abolished the relaxant responses to glyceryl trinitrate, isosorbide dinitrate and nitroprusside; each of these drugs requires activation in the tissue (by enzymes or reducing agents) to generate NO. In contrast, ODQ (3 \u03bcM) caused a parallel shift in the concentration-relaxation curves to linsidomine (SIN-1), FK409, MAHMA NONOate and spermine NONOate (1.63 to 2.54 log units) with no depression in maximum response; each of these NO donors generates NO in the physiological bathing solution without requiring tissue activation. For the four drugs in this group, the effects of 10 \u03bcM ODQ were not significantly greater than the effects of 3 \u03bcM ODQ; thus there was an ODQ-resistant component to the response suggesting that part of the response involved a mechanism that was independent of soluble guanylate cyclase.<\/jats:p>\n               <jats:p>NO donors that require tissue activation probably generate NO within the smooth-muscle cell, whereas those that do not require tissue activation generate NO outside the cell. Hence it is concluded that the site of NO generation (intra- or extracellular) might determine whether or not there is an ODQ-resistant component in the relaxation response.<\/jats:p>","DOI":"10.1211\/0022357991772240","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T23:43:52Z","timestamp":1058571832000},"page":"135-139","source":"Crossref","is-referenced-by-count":37,"title":["Inhibition by 1<i>H<\/i>-[1,2,4]Oxadiazolo[4,3-<i>a<\/i>]quinoxalin-1-one (ODQ) of Responses to Nitric Oxide-donors in Rat Pulmonary Artery: Influence of the Mechanism of Nitric Oxide Generation"],"prefix":"10.1093","volume":"51","author":[{"given":"Kerry L","family":"Homer","sequence":"first","affiliation":[{"name":"Pulmonary Pharmacology Group, Department of Physiology and Pharmacology, The University of Queensland , St Lucia, Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A","family":"Fiore","sequence":"additional","affiliation":[{"name":"Pulmonary Pharmacology Group, Department of Physiology and Pharmacology, The University of Queensland , St Lucia, Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet C","family":"Wanstall","sequence":"additional","affiliation":[{"name":"Pulmonary Pharmacology Group, Department of Physiology and Pharmacology, The University of Queensland , St Lucia, Brisbane, Queensland 4072,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1999,2,1]]},"reference":[{"key":"2024103110043568000_cit1","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/368850a0","article-title":"Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle","volume":"368","author":"Bolotina","year":"1994","journal-title":"Nature"},{"key":"2024103110043568000_cit2","first-page":"48","article-title":"Novel guanylyl cyclase inhibitor potently inhibits cyclic GMP accumulation in endothelial cells and relaxation of bovine pulmonary artery","volume":"277","author":"Brunner","year":"1995","journal-title":"J. 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