{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:40:18Z","timestamp":1762674018942},"reference-count":26,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:p> In estrogen-depleted [i.e., ovariectomized (Ovx)] animals, an endothelium-derived hyperpolarizing factor (EDHF)-like mechanism may arise to, at least partially, replace endothelial nitric oxide (NO) synthase (eNOS)-derived NO in modulating cerebral arteriolar tone. Additional findings show that eNOS expression and function is restored in estrogen-treated Ovx female rats, while the nascent EDHF-like activity disappears. Because NO has been linked to repression of EDHF activity in the periphery, the current study was undertaken to examine whether the nascent EDHF role in cerebral vessels of Ovx females relates to a chronically repressed eNOS-derived NO-generating function. We compared the effects of chronic NOS inhibition with N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine-methyl ester (l-NAME; 100 mg \u00b7 kg<jats:sup>\u20131<\/jats:sup> \u00b7 day<jats:sup>\u20131<\/jats:sup> for 3 wk) on EDHF-mediated pial arteriolar vasodilation in anesthetized intact, Ovx, and 17\u03b2-estradiol-treated (0.1 mg \u00b7 kg<jats:sup>\u20131<\/jats:sup> \u00b7 day<jats:sup>\u20131<\/jats:sup> ip, 1 wk) Ovx (OVE) female rats as well as in male rats that were prepared with closed cranial windows. In the chronic NOS inhibition groups, pial arteriolar responses were monitored in the absence (all groups) and presence (females only) of indomethacin (Indo; 10 mg\/kg iv). Finally, the gap junction inhibitory peptide Gap 27 (300 \u03bcM) was applied to block EDHF-related vasodilation. NO donor ( S-nitroso- N-acetyl-penicillamine) responses were similar in all rats studied. Acetylcholine (ACh) reactivity was virtually absent in control Ovx rats and chronically NOS-inhibited intact female, OVE, and male rats. However, a partial recovery of ACh reactivity was seen in l-NAME-treated Ovx females. In addition, in the presence of l-NAME, a normal CO<jats:sub>2<\/jats:sub> reactivity was observed in all females, whereas a 50% reduction in CO<jats:sub>2<\/jats:sub> reactivity was seen in males. In intact and OVE rats, both chronic and acute ( N<jats:sup>G<\/jats:sup>-nitro-l-arginine suffusion) NOS inhibition, combined with Indo, depressed ADP-induced dilation by \u226550%, and subsequent application of Gap 27 had no further effect on ADP-induced vasodilation. ADP reactivity was retained in Ovx rats after combined chronic NOS inhibition and acute Indo, but was attenuated significantly by Gap 27. In males, Gap 27 had no effect on arteriolar reactivity. Taken together, our data demonstrate that in the cerebral microcirculation, NO does not have an inhibitory effect on EDHF production or action. The increased EDHF-like function in chronic estrogen-depleted animals is not due to eNOS deficiency, suggesting a more direct effect of estrogen in modulating EDHF-mediated cerebral vasodilation. <\/jats:p>","DOI":"10.1152\/ajpheart.00439.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:13:37Z","timestamp":1425413617000},"page":"H2045-H2053","source":"Crossref","is-referenced-by-count":9,"title":["Nascent EDHF-mediated cerebral vasodilation in ovariectomized rats is not induced by eNOS dysfunction"],"prefix":"10.1152","volume":"285","author":[{"given":"H. L.","family":"Xu","sequence":"first","affiliation":[{"name":"Neuroanesthesia Research Laboratory, Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. A.","family":"Santizo","sequence":"additional","affiliation":[{"name":"Neuroanesthesia Research Laboratory, Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. L.","family":"Baughman","sequence":"additional","affiliation":[{"name":"Neuroanesthesia Research Laboratory, Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. A.","family":"Pelligrino","sequence":"additional","affiliation":[{"name":"Neuroanesthesia Research Laboratory, Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois 60607"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.12.3341"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)02050-3"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.6.H2441"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.2.259"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.6.H2417"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701109"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900018"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.6.H2462"},{"key":"REF9","unstructured":"Kontos HA, Wei EP, Ellis EF, Dietrich WD, and Povlishock JT. Prostaglandins in physiological and in certain pathological responses of the cerebral circulation. Fed Proc 40: 2326\u20132330, 1981."},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.57.5.689"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.30.10.2186"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.2.H411"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.2.H459"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01105-6"},{"key":"REF15","unstructured":"Pelligrino DA, Xu HL, and Santizo RA. Role of the glia limitans (GL) in the regulation of pial arteriolar relaxation in ovariectomized (OVX) vs. intact female rats (Abstract). Soc Neurosci 28: 581.18, 2002."},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2206"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00583.2001"},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(01)01292-9"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.3.288"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2002.03632.x"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1994.126"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00024.2001"},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200108000-00002"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00031.2002"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.5.H2105"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.30.5.1125"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00439.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T18:34:05Z","timestamp":1567967645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00439.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,11]]}},"alternative-id":["10.1152\/ajpheart.00439.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00439.2003","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11]]}}}