{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:40:44Z","timestamp":1791276044344,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,2]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>Continuous production of nitric oxide (NO) from endothelial cells permanently inhibits the synthesis and the vasoconstrictor effects of endothelin. Thus, inhibition of NO synthesis might unmask a vasopressor response to endothelin. To assess whether endothelin contributes to the pressor response induced by inhibition of NO synthesis, we tested whether bosentan, a nonpeptide antagonist of ET<jats:sub>A<\/jats:sub>and ET<jats:sub>B<\/jats:sub>endothelin receptors, affected the hypertensive response induced by the NO synthase inhibitor<jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>-nitro<jats:sc>l<\/jats:sc>-arginine methyl ester (L-NAME).<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>Anesthetized rats received increasing doses of L-NAME (0.1 to 3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>) in the absence or the presence of bosentan (3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>IV 15 minutes before L-NAME). Bosentan itself did not affect blood pressure. L-NAME induced a dose-dependent increase in mean arterial pressure (percent increase from baseline after 3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>, 25\u00b15%), and this was reduced by bosentan (13\u00b13%;<jats:italic>P<\/jats:italic>&lt;.05) or by the selective ET<jats:sub>A<\/jats:sub>antagonist BQ-123 (3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>: controls, 25\u00b14%; BQ-123, 14\u00b15%;<jats:italic>P<\/jats:italic>&lt;.01). In contrast, bosentan did not affect the pressor response to phenylephrine (1 to 100 \u03bcg \u00b7 kg<jats:sup>\u22121<\/jats:sup>). The response to L-NAME (3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>) was also reduced by bosentan in ganglion-blocked (chlorisondamine 2.5 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>: controls, 89\u00b110%; bosentan, 45\u00b17%) or pithed rats (controls, 165\u00b19%; bosentan, 85\u00b112%;<jats:italic>P<\/jats:italic>&lt;.01). Bosentan also inhibited the pressor response to another inhibitor of NO synthesis,<jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>-nitro<jats:sc>l<\/jats:sc>-arginine (3 mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>) in normal (controls, 24\u00b15%; bosentan, 10\u00b13%;<jats:italic>P<\/jats:italic>&lt;.01) or ganglion-blocked (controls, 86\u00b113%; bosentan, 25\u00b18%;<jats:italic>P<\/jats:italic>&lt;.01) rats. Finally, L-NAME induced a modest increase in plasma levels of endothelin-1 (controls, 26.8\u00b14.1 pg \u00b7 mL<jats:sup>\u22121<\/jats:sup>; L-NAME, 38.5\u00b13.3 pg \u00b7 mL<jats:sup>\u22121<\/jats:sup>;<jats:italic>P<\/jats:italic>&lt;.05).<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>These experiments demonstrate that inhibition of NO synthesis unmasks a tonic pressor influence of endothelin, suggesting that this peptide could play a major role in pathophysiological situations associated with an impaired formation of NO.<\/jats:p>","DOI":"10.1161\/01.cir.91.3.771","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"771-775","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":121,"title":["In Vivo Evidence of an Endothelin-Induced Vasopressor Tone After Inhibition of Nitric Oxide Synthesis in Rats"],"prefix":"10.1161","volume":"91","author":[{"given":"Vincent","family":"Richard","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen University Hospital, France (V.R., M.H., C.T.), and the Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland (M.C., B-M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Hogie","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen University Hospital, France (V.R., M.H., C.T.), and the Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland (M.C., B-M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Clozel","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen University Hospital, France (V.R., M.H., C.T.), and the Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland (M.C., B-M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd-Michael","family":"Lo\u0308ffler","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen University Hospital, France (V.R., M.H., C.T.), and the Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland (M.C., B-M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Thuillez","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen University Hospital, France (V.R., M.H., C.T.), and the Pharma Division, Preclinical Research, F. 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