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Using isolated rat thoracic aortic rings that were precontracted with phenylephrine, we examined vasodilatory responses to acetylcholine, histamine, and Ca<jats:sup>2+<\/jats:sup>ionophore A23187 (in endothelium-intact rings) and sodium nitroprusside and isoproterenol (in endothelium-denuded rings) in the presence and absence of indigo carmine. In addition, the effects of methylene blue on the acetylcholine- and sodium nitroprusside\u2013induced vasodilation were compared with those of indigo carmine. Indigo carmine (10<jats:sup>\u22126<\/jats:sup>, 10<jats:sup>\u22125<\/jats:sup>, and 10<jats:sup>\u22124<\/jats:sup>mol\/L) significantly inhibited receptor- and non\u2013receptor-mediated endothelium-dependent vasorelaxation. Indigo carmine (10<jats:sup>\u22124<\/jats:sup>mol\/L) also inhibited endothelium-independent vasorelaxation induced by sodium nitroprusside (an activator of vascular smooth muscle soluble guanylyl cyclase), although to a lesser extent than vasodilation from acetylcholine, histamine, and Ca<jats:sup>2+<\/jats:sup>ionophore A23187. In contrast, indigo carmine (10<jats:sup>\u22124<\/jats:sup>mol\/L) had no effect on the vasodilation induced by isoproterenol (an activator of adenylyl cyclase), indicating that indigo carmine selectively inhibits nitric oxide\u2013mediated responses. Methylene blue, a known inhibitor of soluble guanylyl cyclase, inhibited both acetylcholine- and sodium nitroprusside\u2013induced vasorelaxation. The inhibition was also greater in the acetylcholine- than the sodium nitroprusside\u2013induced vasodilation. These results suggest that indigo carmine, like methylene blue, may inhibit endothelium-dependent relaxation by a mechanism that involves two levels. The major action of indigo carmine appears to be at the level of nitric oxide generation and\/or release from the endothelial cell. In addition, indigo carmine appears to inhibit vascular smooth muscle guanylyl cyclase. Thus, indigo carmine may elevate blood pressure by interfering with these nitric oxide\u2013mediated vasodilatory mechanisms.<\/jats:p>","DOI":"10.1161\/01.hyp.27.2.228","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"228-234","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Indigo Carmine Inhibits Endothelium-Dependent and -Independent Vasodilation"],"prefix":"10.1161","volume":"27","author":[{"given":"Kyoung S.K.","family":"Chang","sequence":"first","affiliation":[{"name":"From the Department of Anesthesiology, Oregon Health Sciences University and Anesthesiology Service, Veterans Affairs Medical Center, Portland, Ore."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Z.","family":"Zhong","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology, Oregon Health Sciences University and Anesthesiology Service, Veterans Affairs Medical Center, Portland, Ore."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard F.","family":"Davis","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology, Oregon Health Sciences University and Anesthesiology Service, Veterans Affairs Medical Center, Portland, Ore."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)58715-7"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-4295(77)90192-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-196801000-00078"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)62624-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.3.9.2545495"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0031-6997(25)06663-3","volume":"43","year":"1991","unstructured":"Moncada S, Palmer RMJ, Higgs EA. 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