{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:43:22Z","timestamp":1789825402461,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2677,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>To further investigate into the mechanisms of PAF\u2010induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor <jats:sc>L<\/jats:sc>\u2010N<jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine (<jats:sc>L<\/jats:sc>\u2010NNA), of the specific cyclooxygenase\u20102 (COX\u20102) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea\u2010pig (HLP).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In HLPs perfused with homologous blood, dose\u2010response curves for the haemodynamic and bronchial effects of PAF (1\u2003\u2013\u200332\u2003ng) were carried out in the absence or presence of <jats:sc>L<\/jats:sc>\u2010NNA (200\u2003\u03bc<jats:sc>M<\/jats:sc>). <jats:sc>L<\/jats:sc>\u2010NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF\u2010induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of <jats:sc>L<\/jats:sc>\u2010NNA were antagonized by <jats:sc>L<\/jats:sc>\u2010arginine (2\u2003m<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The presence of <jats:sc>L<\/jats:sc>\u2010NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A<jats:sub>2<\/jats:sub> mimetic U46619 (0.05\u2003\u2013\u20031.6\u2003\u03bcg), 5\u2010hydroxytryptamine (0.1\u2003\u2013\u20031.6\u2003\u03bcg), and histamine (0.1\u2003\u2013\u20031.6\u2003\u03bcg), thus suggesting that these PAF secondary mediators are not responsible for the hyper\u2010responsiveness to PAF induced by <jats:sc>L<\/jats:sc>\u2010NNA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Blocking COX\u20102 pathway with NS 398 (15\u2003\u2013\u200330\u2003\u03bc<jats:sc>M<\/jats:sc>) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF\u2010mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When <jats:sc>L<\/jats:sc>\u2010NNA was added to the perfusing medium of HLPs pre\u2010treated with NS 398 or with indomethacin (15\u2003\u03bc<jats:sc>M<\/jats:sc>), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX\u20102 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX\u20102, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 777\u2013788; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704311\">10.1038\/sj.bjp.0704311<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704311","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T22:04:01Z","timestamp":1106949841000},"page":"777-788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Nitric oxide (NO) modulation of PAF\u2010induced cardiopulmonary action: interaction between NO synthase and cyclo\u2010oxygenase\u20102 pathways"],"prefix":"10.1111","volume":"134","author":[{"given":"Fulvia","family":"Fabi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Calabrese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Stati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Del Basso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-3278(94)90008-6"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-3278(95)90064-0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/5.5.476"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb14926.x"},{"key":"e_1_2_6_6_1","first-page":"2492","article-title":"Platelet\u2010activating factor induces cyclooxygenase\u20102 gene expression in corneal epithelium. 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