{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T16:25:25Z","timestamp":1769012725319,"version":"3.49.0"},"reference-count":57,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n                    Female sexual function is under\u2010studied, and mechanisms of clitoral engorgement\u2010relaxation are incompletely understood. Penile erection results from nitric oxide (NO) \u2010induced cyclic guanosine monophosphate (cGMP) accumulation. cGMP\u2010dependent protein kinase (PKG) activates large\u2010conductance, calcium\u2010activated potassium channels (BK\n                    <jats:sub>Ca<\/jats:sub>\n                    ), thereby hyperpolarizing and relaxing vascular and trabecular smooth muscle cells, allowing engorgement. We hypothesize rat clitorises relax by a similar mechanism. Rat clitorises express components of the proposed pathway: neuronal and endothelial NO synthases, soluble guanylyl cyclase (sGC), type 5 phosphodiesterase (PDE\u20105), and BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels. The NO donor diethylamine NONOate (DEANO), the PKG activator 8\u2010pCPT\u2010cGMP, and the PDE\u20105 inhibitor sildenafil, cause dose\u2010dependent clitoral relaxation that is inhibited by antagonists of PKG (Rp\u20108\u2010Br\u2010cGMPS) or BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels (iberiotoxin). Electrical field stimulation induces tetrodotoxin\u2010sensitive NO release and relaxation that is inhibited by the Na\n                    <jats:sup>+<\/jats:sup>\n                    channel blocker tetrodotoxin or sGC inhibitor\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010(1,2,4)oxadiozolo(4,3\u2010a)quinoxalin\u20101\u2010one. Human BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels, transferred to Chinese hamster ovary cells via an adenoviral vector, and endogenous rat clitoral smooth muscle K\n                    <jats:sup>+<\/jats:sup>\n                    current are activated by this PKG\u2010dependent mechanism. Laser confocal microscopy reveals protein expression of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels on clitoral smooth muscle cells; these cells exhibit BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channel activity that is activated by both DEANO and sildenafil. We conclude that neurovascular derived NO causes clitoral relaxation via a PKG\u2010dependent activation of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels. The BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channel is an appealing target for drug therapy of female erectile dysfunction.\u2014 Gragasin, F. S., Michelakis, E. D., Hogan, A., Moudgil, R., Hashimoto, K., Wu, X., Bonnet, S., Haromy, A., Archer, S. L. The neurovascular mechanism of clitoral erection: nitric oxide and cGMP\u2010stimulated activation of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    channels.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    18, 1382\u20101391 (2004)\n                  <\/jats:p>","DOI":"10.1096\/fj.04-1978com","type":"journal-article","created":{"date-parts":[[2004,8,27]],"date-time":"2004-08-27T18:40:37Z","timestamp":1093632037000},"page":"1382-1391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["The neurovascular mechanism of clitoral erection: nitric oxide and cGMP\u2010stimulated activation of BK\n                    <sub>Ca<\/sub>\n                    channels"],"prefix":"10.1096","volume":"18","author":[{"given":"Ferrante S.","family":"Gragasin","sequence":"first","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelos D.","family":"Michelakis","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angie","family":"Hogan","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Moudgil","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xichen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Al","family":"Haromy","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L.","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology) and the Vascular Biology Group University of Alberta Edmonton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3900468"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.1994.35.3.308"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)92168-Y"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702278"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.1.C299"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7583"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.2.H600"},{"key":"e_1_2_5_9_1","doi-asserted-by":"crossref","DOI":"10.1016\/S0002-9149(99)00042-9","article-title":"Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function and the contractile responses of trabeculae carneae and aortic rings in vitro","volume":"83","author":"Wallis R.","year":"1999","journal-title":"Am. 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