{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:04:39Z","timestamp":1773421479921,"version":"3.50.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p> We have recently demonstrated that endothelium-derived hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) is an endothelium-derived hyperpolarizing factor and that endothelial Cu\/Zn-superoxide dismutase (SOD) plays an important role in the synthesis of endogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in both animals and humans. We examined whether SOD plays a role in the synthesis of endogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> during in vivo reactive hyperemia (RH), an important regulatory mechanism. Mesenteric arterioles from wild-type and Cu,Zn-SOD<jats:sup>\u2212\/\u2212<\/jats:sup> mice were continuously observed by a pencil-type charge-coupled device (CCD) intravital microscope during RH (reperfusion after 20 and 60 s of mesenteric artery occlusion) in the cyclooxygenase blockade under the following four conditions: control, catalase alone, N<jats:sup>G<\/jats:sup>-monomethyl-l-arginine (l-NMMA) alone, and l-NMMA + catalase. Vasodilatation during RH was significantly decreased by catalase or l-NMMA alone and was almost completely inhibited by l-NMMA + catalase in wild-type mice, whereas it was inhibited by l-NMMA and l-NMMA + catalase in the Cu,Zn-SOD<jats:sup>\u2212\/\u2212<\/jats:sup> mice. RH-induced increase in blood flow after l-NMMA was significantly increased in the wild-type mice, whereas it was significantly reduced in the Cu,Zn-SOD<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In mesenteric arterioles of the Cu,Zn-SOD<jats:sup>\u2212\/\u2212<\/jats:sup> mice, Tempol, an SOD mimetic, significantly increased the ACh-induced vasodilatation, and the enhancing effect of Tempol was decreased by catalase. Vascular H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production by fluorescent microscopy in mesenteric arterioles after RH was significantly increased in response to ACh in wild-type mice but markedly impaired in Cu,Zn-SOD<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Endothelial Cu,Zn-SOD plays an important role in the synthesis of endogenous H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> that contributes to RH in mouse mesenteric smaller arterioles. <\/jats:p>","DOI":"10.1152\/ajpheart.01021.2007","type":"journal-article","created":{"date-parts":[[2007,11,17]],"date-time":"2007-11-17T01:45:55Z","timestamp":1195263955000},"page":"H441-H448","source":"Crossref","is-referenced-by-count":17,"title":["Role of Cu,Zn-SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo"],"prefix":"10.1152","volume":"294","author":[{"given":"Toyotaka","family":"Yada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Shimokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Morikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Takaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiro","family":"Shinozaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidezo","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Ogasawara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Kajiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12569.x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb17172.x"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.3.415"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1988.tb11752.x"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00968.2006"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Coffman JD, Gregg DE. 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