{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T22:10:08Z","timestamp":1743372608830,"version":"3.40.3"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1996,7]]},"abstract":"<jats:p>Bovine coronary arteries relax in response to bradykinin, methacholine, sodium nitroprusside, isoproterenol, and arachidonic acid in a concentration-dependent manner. The relaxations to methacholine, bradykinin, and arachidonic acid are lost when endothelium is removed. Indomethacin, a cyclooxygenase inhibitor, attenuated the relaxations to methacholine, bradykinin, and arachidonic acid and shifted the EC<jats:sub>50<\/jats:sub>(control versus indomethacin) to each (1\u00d710<jats:sup>\u22127<\/jats:sup>versus 3\u00d710<jats:sup>\u22127<\/jats:sup>mol\/L, 3\u00d710<jats:sup>\u221210<\/jats:sup>versus 2\u00d710<jats:sup>\u22129<\/jats:sup>mol\/L, and 3\u00d710<jats:sup>\u22127<\/jats:sup>versus 2\u00d710<jats:sup>\u22126<\/jats:sup>mol\/L, respectively). Nitro-<jats:sc>l<\/jats:sc>-arginine, a nitric oxide synthase inhibitor, also attenuated the relaxations to methacholine, bradykinin, and arachidonic acid and shifted the EC<jats:sub>50<\/jats:sub>(control versus nitro-<jats:sc>l<\/jats:sc>-arginine) to each (1\u00d710<jats:sup>\u22127<\/jats:sup>versus 3\u00d710<jats:sup>\u22127<\/jats:sup>mol\/L, 3\u00d710<jats:sup>\u221210<\/jats:sup>versus &gt;10<jats:sup>\u22129<\/jats:sup>mol\/L, and 3\u00d710<jats:sup>\u22127<\/jats:sup>versus &gt;10<jats:sup>\u22126<\/jats:sup>mol\/L, respectively). The combination of indomethacin and nitro-<jats:sc>l<\/jats:sc>-arginine blunted the relaxations to these agents and also shifted the EC<jats:sub>50<\/jats:sub>values (control versus indomethacin plus nitro-<jats:sc>l<\/jats:sc>-arginine) to each (1\u00d710<jats:sup>\u2212<\/jats:sup><jats:sup>7<\/jats:sup>versus 5\u00d710<jats:sup>\u2212<\/jats:sup><jats:sup>7<\/jats:sup>mol\/L, 3\u00d710<jats:sup>\u2212<\/jats:sup><jats:sup>10<\/jats:sup>versus &gt;10<jats:sup>\u2212<\/jats:sup><jats:sup>9<\/jats:sup>mol\/L, and 3\u00d710<jats:sup>\u2212<\/jats:sup><jats:sup>7<\/jats:sup>versus &gt;10<jats:sup>\u2212<\/jats:sup><jats:sup>6<\/jats:sup>mol\/L, respectively). Methacholine, bradykinin, and arachidonic acid stimulated the release of prostaglandin I<jats:sub>2<\/jats:sub>, measured as 6-keto-PGF<jats:sub>1<\/jats:sub><jats:sub>\u03b1<\/jats:sub>. Indomethacin, but not nitro-<jats:sc>l<\/jats:sc>-arginine, inhibited arachidonic acid\u2013induced release of 6-keto-PGF<jats:sub>1<\/jats:sub><jats:sub>\u03b1<\/jats:sub>. Vascular cGMP content was unchanged by arachidonic acid but was significantly elevated by bradykinin. Relaxations to prostaglandin I<jats:sub>2<\/jats:sub>and sodium nitroprusside, but not 8,9-epoxyeicosatrienoic acid or isoproterenol, were inhibited by nitro-<jats:sc>l<\/jats:sc>-arginine. We conclude that the endothelium-dependent relaxations to methacholine, bradykinin, and arachidonic acid are partly due to prostaglandin I<jats:sub>2<\/jats:sub>release. The remainder of the responses to these agents is due to the release of other relaxing factor or factors. Since bradykinin increased cGMP and nitro-<jats:sc>l<\/jats:sc>-arginine partially inhibited its relaxant effects, nitric oxide also appears to participate in the bradykinin-induced effect. Since the combination of indomethacin and nitro-<jats:sc>l<\/jats:sc>-arginine failed to completely block the relaxations to methacholine, bradykinin, and arachidonic acid, another endothelial factor must contribute to their vascular effects. Surprisingly, nitro-<jats:sc>l<\/jats:sc>-arginine attenuated the relaxations to arachidonic acid; however,<jats:sc>l<\/jats:sc>-arginine failed to reverse the effects of nitro-<jats:sc>l<\/jats:sc>-arginine on arachidonic acid\u2013induced relaxations. In addition, arachidonic acid failed to increase cGMP. Nitro-<jats:sc>l<\/jats:sc>-arginine also reduced the responses to prostaglandin I<jats:sub>2<\/jats:sub>and sodium nitroprusside. These data indicate that these arginine analogues may have effects other than competitive inhibition of nitric oxide synthase.<\/jats:p>","DOI":"10.1161\/01.hyp.28.1.76","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"76-82","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Mediators of Arachidonic Acid\u2013Induced Relaxation of Bovine Coronary Artery"],"prefix":"10.1161","volume":"28","author":[{"given":"Phillip F.","family":"Pratt","sequence":"first","affiliation":[{"name":"the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Rosolowsky","sequence":"additional","affiliation":[{"name":"the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William B.","family":"Campbell","sequence":"additional","affiliation":[{"name":"the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.53.5.557"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(76)90125-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(77)90037-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75215-6"},{"key":"e_1_3_2_5_2","first-page":"145","volume":"24","year":"1987","unstructured":"Furchgott RF, Carvalho MH, Khan MT, Matsunaga K. 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