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Arterial segments were isolated and mounted on a microvessel myograph.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>\u2014Inhibition of nitric oxide (NO) formation with<jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>-nitro-<jats:sc>l-<\/jats:sc>arginine (L-NA, 100 \u03bcmol\/L) increased basal tone by 7\u00b11%E<jats:sub>max<\/jats:sub>(n=5). This increase in tone was fully abolished in the presence of BQ123 (1 \u03bcmol\/L; ET<jats:sub>A<\/jats:sub>receptor antagonist,<jats:italic>P<\/jats:italic>&lt;.05) but potentiated by a subthreshold concentration of exogenous ET (1 nmol\/L; 33\u00b18%E<jats:sub>max<\/jats:sub>;<jats:italic>P<\/jats:italic>&lt;.05). In the presence of L-NA, serotonin (10 \u03bcmol\/L)\u2013induced tone was doubled compared with the control response (<jats:italic>P<\/jats:italic>&lt;.05) but reduced by 90% in the presence of BQ123 (<jats:italic>P<\/jats:italic>&lt;.05). In the absence of L-NA, BQ123 prevented serotonin-induced tone (n=3). Oxymetazoline, a selective \u03b1<jats:sub>2<\/jats:sub>-adrenergic receptor agonist, induced an endothelium-dependent relaxation of preconstricted human pial arteries. The relaxation was partially sensitive to NO synthase inhibition and fully prevented by the addition of ET, whereas substance P\u2013induced relaxation was preserved. Glibenclamide (1 \u03bcmol\/L), an inhibitor of ATP-sensitive K<jats:sup>+<\/jats:sup>channels and tetraethylammonium (1 mmol\/L), an inhibitor of Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>channels had no effect on oxymetazoline-induced relaxation.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014The results of this study suggest first that ET is involved in the tonic response induced by NO synthase inhibition; second, part of the contractile response induced by serotonin is endothelium-dependent and sensitive to BQ123; and third, the data suggest that activation of \u03b1<jats:sub>2<\/jats:sub>-adrenergic receptors generated an endothelium-dependent relaxation that was selectively inhibited by exogenous ET.<\/jats:p>","DOI":"10.1161\/01.str.29.1.175","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:08:03Z","timestamp":1308341283000},"page":"175-180","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Control of Vascular Tone by Endogenous Endothelin-1 in Human Pial Arteries"],"prefix":"10.1161","volume":"29","author":[{"given":"Eric","family":"Thorin","sequence":"first","affiliation":[{"name":"From the Institut de Cardiologie de Montre\u0301al, Centre de Recherche (E.T., T.-D.N.), Montreal, and De\u0301partement de Neurochirurgie, Ho\u0302pital Notre-Dame, Montre\u0301al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh-Dung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Montre\u0301al, Centre de Recherche (E.T., T.-D.N.), Montreal, and De\u0301partement de Neurochirurgie, Ho\u0302pital Notre-Dame, Montre\u0301al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Bouthillier","sequence":"additional","affiliation":[{"name":"From the Institut de Cardiologie de Montre\u0301al, Centre de Recherche (E.T., T.-D.N.), Montreal, and De\u0301partement de Neurochirurgie, Ho\u0302pital Notre-Dame, Montre\u0301al, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.18.6964"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)54489-6"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.70.6.1315634"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)92679-X"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(94)90120-1"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.4.830"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.26.1.83"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.19.2.131"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.14.6344"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)91198-2"},{"key":"e_1_3_1_12_2","first-page":"656","volume":"354","year":"1996","unstructured":"Petersson J, Hanson GC, Lindberg BF, H\u00f6gest\u00e4tt ED. 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