{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T06:56:07Z","timestamp":1791701767924,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economy and Competitiveness","award":["PI15\/01160"],"award-info":[{"award-number":["PI15\/01160"]}]},{"name":"Ministry of Economy and Competitiveness","award":["PI20\/00977"],"award-info":[{"award-number":["PI20\/00977"]}]},{"name":"Ministry of Economy and Competitiveness","award":["PI23\/00877"],"award-info":[{"award-number":["PI23\/00877"]}]},{"name":"Ministry of Economy and Competitiveness","award":["CIBERFES CB16\/10\/00464"],"award-info":[{"award-number":["CIBERFES CB16\/10\/00464"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO\/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKC\u03b22 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO\/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.<\/jats:p>","DOI":"10.3390\/ijms25063111","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:33:06Z","timestamp":1709811186000},"page":"3111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PKC Inhibition Improves Human Penile Vascular Function and the NO\/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5390-5677","authenticated-orcid":false,"given":"Mariam","family":"El Assar","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital de Getafe, 28905 Getafe, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"La Fuente","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Urologia, Centro Hospitalar e Universit\u00e1rio de Santo Ant\u00f3nio (CHUdSA), 4099-001 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Sosa","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital de Getafe, 28905 Getafe, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argentina","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda\u2014IRYCIS\/UFV, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto J.","family":"Pepe-Cardoso","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Urologia, Hospital Fernando da Fonseca, 2720-276 Amadora, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2318-9064","authenticated-orcid":false,"given":"Juan I.","family":"Mart\u00ednez-Salamanca","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitario Puerta de Hierro, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-1333","authenticated-orcid":false,"given":"Leocadio","family":"Rodr\u00edguez-Ma\u00f1as","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28029 Madrid, Spain"},{"name":"Servicio de Geriatr\u00eda, Hospital Universitario de Getafe, 28905 Getafe, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-9465","authenticated-orcid":false,"given":"Javier","family":"Angulo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda\u2014IRYCIS\/UFV, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","article-title":"IDF Diabetes Atlas: Global Estimates for the Prevalence of Diabetes for 2015 and 2040","volume":"128","author":"Ogurtsova","year":"2017","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e3494","DOI":"10.1002\/dmrr.3494","article-title":"Erectile Dysfunction and Diabetes: A Melting Pot of Circumstances and Treatments","volume":"38","author":"Defeudis","year":"2022","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/andr.13257","article-title":"The Management of Erectile Dysfunction in Men with Diabetes Mellitus Unresponsive to Phosphodiesterase Type 5 Inhibitors","volume":"11","author":"Tharakan","year":"2023","journal-title":"Andrology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113358","DOI":"10.1016\/j.jep.2020.113358","article-title":"Uncovering the Mechanisms of Leech and Centipede Granules in the Treatment of Diabetes Mellitus-Induced Erectile Dysfunction Utilising Network Pharmacology","volume":"265","author":"Ma","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/j.1743-6109.2009.01587.x","article-title":"Diabetes Exacerbates the Functional Deficiency of NO\/CGMP Pathway Associated with Erectile Dysfunction in Human Corpus Cavernosum and Penile Arteries","volume":"7","author":"Angulo","year":"2010","journal-title":"J. Sex. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.jsxm.2022.08.200","article-title":"STIM\/Orai Inhibition as a Strategy for Alleviating Diabetic Erectile Dysfunction through Modulation of Rat and Human Penile Tissue Contractility and In Vivo Potentiation of Erectile Responses","volume":"19","author":"Angulo","year":"2022","journal-title":"J. Sex. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1111\/j.1743-6109.2012.02743.x","article-title":"Flow-Evoked Vasodilation Is Blunted in Penile Arteries from Zucker Diabetic Fatty Rats","volume":"9","author":"Kun","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.bbrc.2003.11.034","article-title":"Diabetes Impairs Endothelium-Dependent Relaxation of Human Penile Vascular Tissues Mediated by NO and EDHF","volume":"312","author":"Angulo","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1006\/bbrc.2001.4874","article-title":"Increased Expression of Arginase II in Human Diabetic Corpus Cavernosum: In Diabetic-Associated Erectile Dysfunction","volume":"283","author":"Bivalacqua","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"716332","DOI":"10.3389\/fphar.2021.716332","article-title":"Potential Role of Protein Kinase C in the Pathophysiology of Diabetes-Associated Atherosclerosis","volume":"12","author":"Lien","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jubaidi, F.F., Zainalabidin, S., Taib, I.S., Abdul Hamid, Z., Mohamad Anuar, N.N., Jalil, J., Mohd Nor, N.A., and Budin, S.B. (2022). The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158582"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0014-2999(03)02113-7","article-title":"Protein Kinase C\u03b2 Inhibition and Aorta and Corpus Cavernosum Function in Streptozotocin-Diabetic Mice","volume":"475","author":"Nangle","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1124\/jpet.106.108597","article-title":"Enhanced Thromboxane Receptor-Mediated Responses and Impaired Endothelium-Dependent Relaxation in Human Corpus Cavernosum from Diabetic Impotent Men: Role of Protein Kinase C Activity","volume":"319","author":"Angulo","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108565","DOI":"10.1016\/j.jdiacomp.2023.108565","article-title":"Protein Kinase C: A Potential Therapeutic Target for Endothelial Dysfunction in Diabetes","volume":"37","author":"Xiao","year":"2023","journal-title":"J. Diabetes Complicat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/nrurol.2016.23","article-title":"Molecular Mechanisms Associated with Diabetic Endothelial-Erectile Dysfunction","volume":"13","author":"Castela","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ijcard.2014.04.117","article-title":"Protein Kinase C in Enhanced Vascular Tone in Diabetes Mellitus","volume":"174","author":"Kizub","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S227","DOI":"10.1097\/01.ASN.0000077407.90309.65","article-title":"Protein Kinase C-Dependent Increase in Reactive Oxygen Species (ROS) Production in Vascular Tissues of Diabetes: Role of Vascular NAD(P)H Oxidase","volume":"14","author":"Inoguchi","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000332337","article-title":"Inhibition of Protein Kinase C \u03b22 Prevents Tumor Necrosis Factor-\u03b1-Induced Apoptosis and Oxidative Stress in Endothelial Cells: The Role of NADPH Oxidase Subunits","volume":"49","author":"Deng","year":"2012","journal-title":"J. Vasc. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ucl.2021.06.009","article-title":"Physiology of Erection and Pathophysiology of Erectile Dysfunction","volume":"48","author":"MacDonald","year":"2021","journal-title":"Urol. Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/17446651.2023.2279533","article-title":"The Vascular Complications of Diabetes: A Review of Their Management, Pathogenesis, and Prevention","volume":"19","author":"Meir","year":"2024","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/2047487319878373","article-title":"The Link between Diabetes and Atherosclerosis","volume":"26","author":"Prattichizzo","year":"2019","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/j.1743-6109.2008.01168.x","article-title":"Erectile Dysfunction in Diabetes Mellitus","volume":"6","author":"Malavige","year":"2009","journal-title":"J. Sex. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/s00125-021-05607-z","article-title":"Differences in the Prevalence of Erectile Dysfunction between Novel Subgroups of Recent-Onset Diabetes","volume":"65","author":"Maalmi","year":"2022","journal-title":"Diabetologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0022-5347(17)34871-1","article-title":"Impotence and Its Medical and Psychosocial Correlates: Results of the Massachusetts Male Aging Study","volume":"151","author":"Feldman","year":"1994","journal-title":"J. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/andr.13132","article-title":"Type 2 Diabetes Mellitus Increases Risk of Erectile Dysfunction Independent of Obesity and Dyslipidemia: A Mendelian Randomization Study","volume":"10","author":"Yuan","year":"2022","journal-title":"Andrology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1279058","DOI":"10.3389\/fendo.2023.1279058","article-title":"Type 2 Diabetes Mellitus and the Risk of Male Infertility: A Mendelian Randomization Study","volume":"14","author":"Zhu","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1007\/s00125-004-1549-6","article-title":"Impact of Diabetes Mellitus on the Severity of Erectile Dysfunction and Response to Treatment: Analysis of Data from Tadalafil Clinical Trials","volume":"47","author":"Fonseca","year":"2004","journal-title":"Diabetologia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e12939","DOI":"10.1111\/ijcp.12939","article-title":"Treatment Response to Sildenafil in Men with Erectile Dysfunction Relative to Concomitant Comorbidities and Age","volume":"71","author":"Goldstein","year":"2017","journal-title":"Int. J. Clin. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1172\/JCI115266","article-title":"A Nitric Oxide-like Factor Mediates Nonadrenergic-Noncholinergic Neurogenic Relaxation of Penile Corpus Cavernosum Smooth Muscle","volume":"88","author":"Kim","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1056\/NEJM199201093260203","article-title":"Nitric Oxide as a Mediator of Relaxation of the Corpus Cavernosum in Response to Nonadrenergic, Noncholinergic Neurotransmission","volume":"326","author":"Rajfer","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1016\/S0022-5347(01)63299-3","article-title":"Effects of Sildenafil on the Relaxation of Human Corpus Cavernosum Tissue In Vitro and on the Activities of Cyclic Nucleotide Phosphodiesterase Isozymes","volume":"159","author":"Ballard","year":"1998","journal-title":"J. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/sj.ijir.3900726","article-title":"The Phosphodiesterase Inhibitory Selectivity and the In Vitro and In Vivo Potency of the New PDE5 Inhibitor Vardenafil","volume":"13","author":"Angulo","year":"2001","journal-title":"Int. J. Impot. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.jsxm.2016.01.016","article-title":"Pharmacotherapy for Erectile Dysfunction: Recommendations from the Fourth International Consultation for Sexual Medicine (ICSM 2015)","volume":"13","author":"Hatzimouratidis","year":"2016","journal-title":"J. Sex. Med."},{"key":"ref_34","first-page":"28","article-title":"The Medical and Surgical Treatment of Erectile Dysfunction: A Review and Update","volume":"27","author":"Karakus","year":"2020","journal-title":"Can. J. Urol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/jsm.12477","article-title":"Nebivolol Potentiates the Efficacy of PDE5 Inhibitors to Relax Corpus Cavernosum and Penile Arteries from Diabetic Patients by Enhancing the NO\/CGMP Pathway","volume":"11","author":"Cardoso","year":"2014","journal-title":"J. Sex. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1161\/CIRCRESAHA.110.217117","article-title":"Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications","volume":"106","author":"Geraldes","year":"2010","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3132\/dvdr.2006.026","article-title":"Protein Kinase C \u03b2 Inhibition: A Novel Therapeutic Strategy for Diabetic Microangiopathy","volume":"3","author":"Idris","year":"2006","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.2337\/diacare.28.11.2686","article-title":"The Effect of Ruboxistaurin on Nephropathy in Type 2 Diabetes","volume":"28","author":"Tuttle","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1167\/iovs.05-0757","article-title":"Inhibition of PKC by Oral Administration of Ruboxistaurin Is Well Tolerated and Ameliorates Diabetes-Induced Retinal Hemodynamic Abnormalities in Patients","volume":"47","author":"Aiello","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"896","DOI":"10.2337\/dc06-1699","article-title":"A 6-Month, Randomized, Double-Masked, Placebo-Controlled Study Evaluating the Effects of the Protein Kinase C-\u03b2 Inhibitor Ruboxistaurin on Skin Microvascular Blood Flow and Other Measures of Diabetic Peripheral Neuropathy","volume":"30","author":"Casellini","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10557-008-6144-5","article-title":"Selective PKC Beta Inhibition with Ruboxistaurin and Endothelial Function in Type-2 Diabetes Mellitus","volume":"23","author":"Mehta","year":"2009","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15771","DOI":"10.1016\/S0021-9258(18)98476-0","article-title":"The Bisindolylmaleimide GF 109203X Is a Potent and Selective Inhibitor of Protein Kinase C","volume":"266","author":"Toullec","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.1016\/S0021-9258(18)98335-3","article-title":"Selective Inhibition of Protein Kinase C Isozymes by the Indolocarbazole G\u00f6 6976","volume":"268","author":"Kazanietz","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/01.CIR.0000133384.38551.A8","article-title":"Selective Inhibition of Protein Kinase Cbeta2 Prevents Acute Effects of High Glucose on Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells","volume":"110","author":"Kouroedov","year":"2004","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1743-6109.2008.01088.x","article-title":"The Novel Antioxidant, AC3056 (2,6-Di-t-Butyl-4-((Dimethyl-4-Methoxyphenylsilyl)Methyloxy)Phenol), Reverses Erectile Dysfunction in Diabetic Rats and Improves NO-Mediated Responses in Penile Tissue from Diabetic Men","volume":"6","author":"Angulo","year":"2009","journal-title":"J. Sex. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.redox.2018.09.025","article-title":"New Insights into Oxidative Stress and Inflammation during Diabetes Mellitus-Accelerated Atherosclerosis","volume":"20","author":"Yuan","year":"2019","journal-title":"Redox Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.2337\/diabetes.52.10.2603","article-title":"Translocation of Glomerular P47phox and P67phox by Protein Kinase C-Beta Activation Is Required for Oxidative Stress in Diabetic Nephropathy","volume":"52","author":"Kitada","year":"2003","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/sj.ijir.3901523","article-title":"Reactive Oxygen Species and Erectile Dysfunction: Possible Role of NADPH Oxidase","volume":"19","author":"Jeremy","year":"2007","journal-title":"Int. J. Impot. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1189\/jlb.0610322","article-title":"Protective Effects of Apocynin, an Inhibitor of NADPH Oxidase Activity, in Splanchnic Artery Occlusion and Reperfusion","volume":"88","author":"Paterniti","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.tem.2014.06.012","article-title":"Endothelial NADPH Oxidases: Which NOX to Target in Vascular Disease?","volume":"25","author":"Drummond","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"752366","DOI":"10.3389\/fphys.2021.752366","article-title":"Effects of Pharmacological Inhibitors of NADPH Oxidase on Myogenic Contractility and Evoked Vasoactive Responses in Rat Resistance Arteries","volume":"12","author":"Kendrick","year":"2022","journal-title":"Front. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3111\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:10:36Z","timestamp":1760105436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063111"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063111","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}