{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:14:48Z","timestamp":1781075688262,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/08122\u20109"],"award-info":[{"award-number":["2017\/08122\u20109"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/18886\u20101"],"award-info":[{"award-number":["2019\/18886\u20101"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with sickle cell disease (SCD) experience intravascular hemolysis, leading to elevated plasma heme levels. This phenomenon has been associated with increased priapism in men with SCD. The heme group can be metabolized by heme oxygenase (HO), generating carbon monoxide (CO), which is known to promote smooth muscle relaxation via soluble guanylyl cyclase (sGC)\u2013cyclic guanosine monophosphate (cGMP). However, the effects of heme on the relaxation responses of corpus cavernosum (CC) have not been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the functional and biochemical effects of the heme group on mouse CC smooth muscle in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Male C57BL\/6 mice were used. CC tissues were mounted in organ baths. Measurement of cGMP in mice CC was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cumulative addition of heme concentrations promoted the relaxation of CC. HO inhibitor (1J, 100\u00a0\u03bcM) or sGC inhibitor (ODQ, 10\u00a0\u03bcM) blocked the relaxing effect of the heme group. Pre\u2010incubation of CC with heme (100\u00a0\u03bcM) enhanced relaxation induced by acetylcholine, sodium nitroprusside, and nitrergic relaxation (electrical field stimulation), which was abolished by 1J or ODQ. The heme group increased the cGMP production in CC, which was abolished by 1J or ODQ. cGMP levels were significantly higher in CC treated with heme, and pre\u2010incubation with compound 1J or ODQ abolished the effect of heme in raising cGMP levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>The HO\u2013CO\u2013sGC\u2013cGMP pathway appears to play a crucial role in promoting CC relaxation. Our study provides novel insight into the role of group heme in CC relaxation and its potential contribution to priapism in SCD. Heme may serve as a pharmacological target for new therapies to prevent priapism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13599","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T17:55:57Z","timestamp":1705514157000},"page":"1857-1864","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Heme\u2010induced corpus cavernosum relaxation and its implications for priapism in sickle cell disease: a mechanistic insight"],"prefix":"10.1111","volume":"12","author":[{"given":"Dalila Andrade","family":"Pereira","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology S\u00e3o Francisco University Medical School  Bragan\u00e7a Paulista, S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danillo Andrade","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology S\u00e3o Francisco University Medical School  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