{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T21:13:36Z","timestamp":1778879616026,"version":"3.51.4"},"reference-count":85,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["315096\/2023-3"],"award-info":[{"award-number":["315096\/2023-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["N\\u00BA 026\/2019"],"award-info":[{"award-number":["N\\u00BA 026\/2019"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004911","name":"Foundation for Research Support of Piau\u00ed State","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF20OC0065767"],"award-info":[{"award-number":["NNF20OC0065767"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006111","name":"Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"publisher","award":["CIRCNA\/BRB\/0281\/2019"],"award-info":[{"award-number":["CIRCNA\/BRB\/0281\/2019"]}],"id":[{"id":"10.13039\/501100006111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006111","name":"Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}],"id":[{"id":"10.13039\/501100006111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016218","name":"Regional Agency for the Development of Research Technology and Innovation","doi-asserted-by":"publisher","award":["PTDC\/BII- BIO \/31158\/2017"],"award-info":[{"award-number":["PTDC\/BII- BIO \/31158\/2017"]}],"id":[{"id":"10.13039\/100016218","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016218","name":"Regional Agency for the Development of Research Technology and Innovation","doi-asserted-by":"publisher","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}],"id":[{"id":"10.13039\/100016218","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007396","name":"Minist\u00e9rio da Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002702","name":"Aalborg Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002702","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.ejphar.2025.177857","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T11:04:29Z","timestamp":1750331069000},"page":"177857","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Functional studies and molecular dynamics reveal BPP-BrachyNH2-induced relaxation in male rat small mesenteric arteries via binding to argininosuccinate synthase"],"prefix":"10.1016","volume":"1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-2744","authenticated-orcid":false,"given":"Daniel Dias","family":"Rufino Arcanjo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isadora Bas\u00edlio","family":"Meneses Bezerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-694X","authenticated-orcid":false,"given":"Sim\u00f3n Gabriel","family":"Comerma-Steffensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-1636","authenticated-orcid":false,"given":"Judit","family":"Prat-Duran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-7281","authenticated-orcid":false,"given":"Daniel Carneiro","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreanne Gomes","family":"Vasconcelos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Pl\u00e1cido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-3781","authenticated-orcid":false,"given":"C\u00e1tia","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Carolina","family":"Cardoso-Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrelina Noronha","family":"Coelho-de-Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9740-5818","authenticated-orcid":false,"given":"Marcelo","family":"Bemquerer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte M\u00f8nster","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5056","authenticated-orcid":false,"given":"Reinhard","family":"Wimmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldeidia","family":"Pereira de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Martins","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-7666","authenticated-orcid":false,"given":"Ulf","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Roberto","family":"de Souza de Almeida Leite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2025.177857_bib1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s10989-016-9564-2","article-title":"In Silico, in vitro and in vivo toxicological assessment of BPP-BrachyNH2, A vasoactive proline-rich oligopeptide from Brachycephalus ephippium","volume":"23","author":"Arcanjo","year":"2017","journal-title":"Int. J. Pept. Res. Therapeut."},{"key":"10.1016\/j.ejphar.2025.177857_bib2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0145071","article-title":"A novel vasoactive proline-rich oligopeptide from the skin secretion of the frog Brachycephalus ephippium","volume":"10","author":"Arcanjo","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2025.177857_bib3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ejmech.2017.08.019","article-title":"Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme","volume":"139","author":"Arcanjo","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib4","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: application to microtubules and the ribosome","volume":"98","author":"Baker","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejphar.2025.177857_bib5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0023680","article-title":"Bothrops jararaca peptide with anti-hypertensive action normalizes endothelium dysfunction involved in physiopathology of Preeclampsia","volume":"6","author":"Benedetti","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2025.177857_bib6","series-title":"Intermolecular Forces, the Jerusalem Symposia on Quantum Chemistry and Biochemistry","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/978-94-015-7658-1_21","article-title":"Interaction models for water in relation to protein hydration","author":"Berendsen","year":"1981"},{"key":"10.1016\/j.ejphar.2025.177857_bib7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11010-017-2994-0","article-title":"Reversal of endothelial dysfunction in aorta of streptozotocin-nicotinamide-induced type-2 diabetic rats by S-Allylcysteine","volume":"432","author":"Brahmanaidu","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.ejphar.2025.177857_bib8","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.toxicon.2011.07.013","article-title":"Bradykinin-potentiating peptides: beyond captopril","volume":"59","author":"Camargo","year":"2012","journal-title":"Toxicon"},{"key":"10.1016\/j.ejphar.2025.177857_bib9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.trsl.2013.09.008","article-title":"Two different approaches to restore renal nitric oxide and prevent hypertension in young spontaneously hypertensive rats: l-citrulline and nitrate","volume":"163","author":"Chien","year":"2014","journal-title":"Transl. Res."},{"key":"10.1016\/j.ejphar.2025.177857_bib10","series-title":"Handbook of Biologically Active Peptides","first-page":"291","article-title":"Bradykinin-Related peptides from frog skin","author":"Conlon","year":"2006"},{"key":"10.1016\/j.ejphar.2025.177857_bib11","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.bbrc.2008.10.056","article-title":"Phosphorylation of argininosuccinate synthase by protein kinase A","volume":"377","author":"Corbin","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2025.177857_bib12","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1021\/acs.jnatprod.3c00991","article-title":"Structural characterization and rat aortic vascular reactivity of bradykinin-potentiating peptides (BPPs) from the snake venom of Bothrops moojeni from Delta do Parna\u00edba Region, Brazil","volume":"87","author":"Costa","year":"2024","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ejphar.2025.177857_bib13","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ccc.2019.12.009","article-title":"Nitric oxide and endothelial dysfunction","volume":"36","author":"Cyr","year":"2020","journal-title":"Crit. Care Clin."},{"key":"10.1016\/j.ejphar.2025.177857_bib14","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: an N \u22c5log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.ejphar.2025.177857_bib15","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1080\/07391102.2022.2035819","article-title":"Computational investigation of the alkaloids of Pilocarpus microphyllus species as phytopharmaceuticals for the inhibition of sterol 14\u03b1-demethylase protease of Trypanosoma cruzi","volume":"41","author":"De S\u00e1","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"10.1016\/j.ejphar.2025.177857_bib16","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/0006-2952(63)90094-7","article-title":"Inhibition in vivo of the enzymatic inactivation of bradykinin and kallidin","volume":"12","author":"Erd\u00f6s","year":"1963","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib17","doi-asserted-by":"crossref","DOI":"10.1002\/0471250953.bi0506s15","article-title":"Comparative protein structure modeling using modeller","volume":"15","author":"Eswar","year":"2006","journal-title":"Curr. Protoc. Bioinforma."},{"key":"10.1016\/j.ejphar.2025.177857_bib18","series-title":"StatPearls","article-title":"Biochemistry, lipopolysaccharide","author":"Farhana","year":"2025"},{"key":"10.1016\/j.ejphar.2025.177857_bib19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1476-5381.1965.tb02091.x","article-title":"A bradykinin\u2010potentiating factor (bpf) present in the venom of Bothrops Jararaca","volume":"24","author":"Ferreira","year":"1965","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"10.1016\/j.ejphar.2025.177857_bib20","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1021\/bi00815a005","article-title":"Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom","volume":"9","author":"Ferreira","year":"1970","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejphar.2025.177857_bib21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/225379a0","article-title":"Activity of various fractions of bradykinin potentiating factor against angiotensin I converting enzyme","volume":"225","author":"Ferreira","year":"1970","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2025.177857_bib22","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/0006-2952(62)90190-9","article-title":"Potentiation of bradykinin by dimercaptopropanol (bal) and other inhibitors of its destroying enzyme in plasma","volume":"11","author":"Ferreira","year":"1962","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib23","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: regulation and function","volume":"33","author":"F\u00f6rstermann","year":"2012","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.ejphar.2025.177857_bib24","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1016\/0040-4020(80)80168-2","article-title":"Iterative partial equalization of orbital electronegativity\u2014a rapid access to atomic charges","volume":"36","author":"Gasteiger","year":"1980","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejphar.2025.177857_bib25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mib.2015.10.005","article-title":"Dual role of arginine metabolism in establishing pathogenesis","volume":"29","author":"Gogoi","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"10.1016\/j.ejphar.2025.177857_bib26","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.bcp.2007.07.014","article-title":"Identification of novel bradykinin-potentiating peptides (BPPs) in the venom gland of a rattlesnake allowed the evaluation of the structure\u2013function relationship of BPPs","volume":"74","author":"Gomes","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib27","doi-asserted-by":"crossref","DOI":"10.1101\/pdb.prot5200","article-title":"Computational docking of biomolecular complexes with AutoDock","volume":"2009","author":"Goodsell","year":"2009","journal-title":"Cold Spring Harb. Protoc."},{"key":"10.1016\/j.ejphar.2025.177857_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1099-1352(199601)9:1<1::AID-JMR241>3.0.CO;2-6","article-title":"Automated docking of flexible ligands: applications of autodock","volume":"9","author":"Goodsell","year":"1996","journal-title":"J. Mol. Recogn."},{"key":"10.1016\/j.ejphar.2025.177857_bib29","doi-asserted-by":"crossref","first-page":"18353","DOI":"10.1074\/jbc.M308160200","article-title":"Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells","volume":"279","author":"Goodwin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib30","doi-asserted-by":"crossref","first-page":"20022","DOI":"10.1074\/jbc.M109.021089","article-title":"Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide","volume":"284","author":"Guerreiro","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbrc.2012.03.074","article-title":"Insulin transcriptionally regulates argininosuccinate synthase to maintain vascular endothelial function","volume":"421","author":"Haines","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2025.177857_bib32","first-page":"8","article-title":"Argininosuccinate synthase: at the center of arginine metabolism","volume":"2","author":"Haines","year":"2011","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"10.1016\/j.ejphar.2025.177857_bib33","series-title":"Handbook of Biologically Active Peptides","first-page":"355","article-title":"Snake venom peptides","author":"Harvey","year":"2006"},{"key":"10.1016\/j.ejphar.2025.177857_bib34","doi-asserted-by":"crossref","first-page":"9405","DOI":"10.1016\/S0021-9258(17)36893-X","article-title":"Argininosuccinate synthetase mRNA and activity are induced by immunostimulants in vascular smooth muscle. Role in the regeneration or arginine for nitric oxide synthesis","volume":"269","author":"Hattori","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib35","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1124\/jpet.115.227017","article-title":"Involvement of potassium channels and calcium-independent mechanisms in hydrogen sulfide\u2013induced relaxation of rat mesenteric small arteries","volume":"356","author":"Hedegaard","year":"2016","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2025.177857_bib36","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.cardiores.2004.01.014","article-title":"Measurements of nitric oxide concentration and hyporeactivity in rat superior mesenteric artery exposed to endotoxin","volume":"62","author":"Hernanz","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.ejphar.2025.177857_bib37","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H","article-title":"LINCS: a linear constraint solver for molecular simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib38","doi-asserted-by":"crossref","first-page":"D368","DOI":"10.1093\/nar\/gkac1050","article-title":"Biological magnetic resonance data bank","volume":"51","author":"Hoch","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejphar.2025.177857_bib39","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.coph.2008.11.007","article-title":"The application of toxins and venoms to cardiovascular drug discovery","volume":"9","author":"Hodgson","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib40","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1046\/j.1432-1033.2003.03559.x","article-title":"Argininosuccinate synthetase from the urea cycle to the citrulline\u2013NO cycle","volume":"270","author":"Husson","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.ejphar.2025.177857_bib41","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1124\/jpet.107.120873","article-title":"Do the cardiovascular effects of angiotensin-converting enzyme (ACE) I involve ACE-Independent mechanisms? New insights from proline-rich peptides of Bothrops jararaca","volume":"322","author":"Ianzer","year":"2007","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2025.177857_bib42","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1124\/pr.120.019240","article-title":"The noncanonical pathway for in vivo nitric oxide generation: the nitrate-nitrite-nitric oxide pathway","volume":"72","author":"Kapil","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.ejphar.2025.177857_bib43","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1107\/S0907444907067455","article-title":"Structure of human argininosuccinate synthetase","volume":"64","author":"Karlberg","year":"2008","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejphar.2025.177857_bib44","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1111\/j.1476-5381.2010.00872.x","article-title":"Animal research: reporting in vivo experiments: the ARRIVE guidelines","volume":"160","author":"Kilkenny","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib45","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"G_mmpbsa \u2014A GROMACS tool for high-throughput MM-PBSA calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejphar.2025.177857_bib46","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1021\/ci200227u","article-title":"LigPlot+: multiple ligand\u2013protein interaction diagrams for drug discovery","volume":"51","author":"Laskowski","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejphar.2025.177857_bib47","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd1197","article-title":"Therapeutic potential of venom peptides","volume":"2","author":"Lewis","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejphar.2025.177857_bib48","author":"Lindahl"},{"key":"10.1016\/j.ejphar.2025.177857_bib49","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/sj.bjp.0705380","article-title":"Extracellular L \u2010arginine is required for optimal NO synthesis by eNOS and iNOS in the rat mesenteric artery wall","volume":"139","author":"MacKenzie","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib50","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jmr.2005.01.017","article-title":"AutoLink: automated sequential resonance assignment of biopolymers from NMR data by relative-hypothesis-prioritization-based simulated logic","volume":"174","author":"Masse","year":"2005","journal-title":"J. Magn. Reson."},{"key":"10.1016\/j.ejphar.2025.177857_bib51","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.ejphar.2025.177857_bib52","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.bcp.2010.12.016","article-title":"Bj-PRO-5a, a natural angiotensin-converting enzyme inhibitor, promotes vasodilatation mediated by both bradykinin B2 and M1 muscarinic acetylcholine receptors","volume":"81","author":"Morais","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib53","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.peptides.2013.07.016","article-title":"Proline rich-oligopeptides: diverse mechanisms for antihypertensive action","volume":"48","author":"Morais","year":"2013","journal-title":"Peptides"},{"key":"10.1016\/j.ejphar.2025.177857_bib54","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function","volume":"19","author":"Morris","year":"1998","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib55","doi-asserted-by":"crossref","DOI":"10.1002\/0471250953.bi0814s24","article-title":"Using AutoDock for ligand\u2010receptor docking","volume":"24","author":"Morris","year":"2008","journal-title":"Curr. Protoc. Bioinforma."},{"key":"10.1016\/j.ejphar.2025.177857_bib56","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1161\/01.RES.41.1.19","article-title":"Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats","volume":"41","author":"Mulvany","year":"1977","journal-title":"Circ. Res."},{"key":"10.1016\/j.ejphar.2025.177857_bib57","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1080\/00268978300102851","article-title":"Constant pressure molecular dynamics for molecular systems","volume":"50","author":"Nos\u00e9","year":"1983","journal-title":"Mol. Phys."},{"key":"10.1016\/j.ejphar.2025.177857_bib58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.peptides.2018.10.005","article-title":"BJ-PRO-7A and BJ-PRO-10C induce vasodilatation and inotropic effects in normotensive and hypertensive rats: role of nitric oxide and muscarinic receptors","volume":"110","author":"Nunes","year":"2018","journal-title":"Peptides"},{"key":"10.1016\/j.ejphar.2025.177857_bib59","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0021-9258(17)42251-4","article-title":"Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell line. Implications for regulation of nitric oxide production","volume":"269","author":"Nussler","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib60","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/sj.bjp.0704079","article-title":"Temporal variation in endotoxin\u2010induced vascular hyporeactivity in a rat mesenteric artery organ culture model","volume":"133","author":"O'Brien","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.177857_bib61","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/bip.22925","article-title":"Ocellatin\u2010 PT antimicrobial peptides: high\u2010resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems","volume":"105","author":"Oliveira","year":"2016","journal-title":"Biopolymers"},{"key":"10.1016\/j.ejphar.2025.177857_bib62","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1002\/jcc.20090","article-title":"A biomolecular force field based on the free enthalpy of hydration and solvation: the GROMOS force\u2010field parameter sets 53A5 and 53A6","volume":"25","author":"Oostenbrink","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib63","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic transitions in single crystals: a new molecular dynamics method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"10.1016\/j.ejphar.2025.177857_bib64","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib65","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/prot.25285","article-title":"Cry1A(b)16 toxin from Bacillus thuringiensis : theoretical refinement of three\u2010dimensional structure and prediction of peptides as molecular markers for detection of genetically modified organisms","volume":"85","author":"Pl\u00e1cido","year":"2017","journal-title":"Proteins Struct. Funct. Bioinforma."},{"key":"10.1016\/j.ejphar.2025.177857_bib66","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1515\/hsz-2019-0368","article-title":"Dr. NO and mr. Toxic \u2013 the versatile role of nitric oxide","volume":"401","author":"Porrini","year":"2020","journal-title":"Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib67","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.addr.2007.09.012","article-title":"Proline-rich, amphipathic cell-penetrating peptides","volume":"60","author":"Pujals","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejphar.2025.177857_bib68","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1007\/s00894-012-1383-6","article-title":"Interaction of wild type, G68R and L125M isoforms of the arylamine-N-acetyltransferase from Mycobacterium tuberculosis with isoniazid: a computational study on a new possible mechanism of resistance","volume":"18","author":"Ramos","year":"2012","journal-title":"J. Mol. Model."},{"key":"10.1016\/j.ejphar.2025.177857_bib69","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"\u0160ali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejphar.2025.177857_bib70","first-page":"57","article-title":"Python: a programming language for software integration and development","volume":"17","author":"Sanner","year":"1999","journal-title":"J. Mol. Graph. Model."},{"key":"10.1016\/j.ejphar.2025.177857_bib71","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1023\/A:1020997118364","article-title":"A software tool for the prediction of Xaa-Pro peptide bond conformations in proteins based on 13C chemical shift statistics","volume":"24","author":"Schubert","year":"2002","journal-title":"J. Biomol. NMR"},{"key":"10.1016\/j.ejphar.2025.177857_bib72","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"Prodrg : a tool for high-throughput crystallography of protein\u2013ligand complexes","volume":"60","author":"Sch\u00fcttelkopf","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.ejphar.2025.177857_bib73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40409-017-0134-7","article-title":"The modular nature of bradykinin-potentiating peptides isolated from snake venoms","volume":"23","author":"Sciani","year":"2017","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"10.1016\/j.ejphar.2025.177857_bib74","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical potential for assessment and prediction of protein structures","volume":"15","author":"Shen","year":"2006","journal-title":"Protein Sci."},{"key":"10.1016\/j.ejphar.2025.177857_bib75","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.toxicon.2007.11.003","article-title":"Tissue distribution in mice of BPP 10c, a potent proline-rich anti-hypertensive peptide of Bothrops jararaca","volume":"51","author":"Silva","year":"2008","journal-title":"Toxicon"},{"key":"10.1016\/j.ejphar.2025.177857_bib76","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1287\/moor.6.1.19","article-title":"Minimization by random search techniques","volume":"6","author":"Solis","year":"1981","journal-title":"Math. Oper. Res."},{"key":"10.1016\/j.ejphar.2025.177857_bib77","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1006\/abio.2000.4880","article-title":"Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set","volume":"287","author":"Sreerama","year":"2000","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ejphar.2025.177857_bib78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00128336","article-title":"MOPAC: a semiempirical molecular orbital program","volume":"4","author":"Stewart","year":"1990","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejphar.2025.177857_bib79","doi-asserted-by":"crossref","first-page":"D609","DOI":"10.1093\/nar\/gkae1010","article-title":"UniProt: the Universal Protein Knowledgebase in 2025","volume":"53","author":"The","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ejphar.2025.177857_bib80","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1038\/s41467-018-04003-3","article-title":"Proteome-wide analysis of cysteine oxidation reveals metabolic sensitivity to redox stress","volume":"9","author":"Van Der Reest","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejphar.2025.177857_bib81","series-title":"NMR of Proteins and Nucleic Acids, the George Fisher Baker Non-resident Lectureship in Chemistry at Cornell University","author":"W\u00fcthrich","year":"1986"},{"key":"10.1016\/j.ejphar.2025.177857_bib82","doi-asserted-by":"crossref","first-page":"16624","DOI":"10.1074\/jbc.272.26.16624","article-title":"Argininosuccinate synthetase overexpression in vascular smooth muscle cells potentiates immunostimulant-induced NO production","volume":"272","author":"Xie","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2025.177857_bib83","first-page":"250","article-title":"ROS-Induced endothelial dysfunction in the pathogenesis of atherosclerosis","volume":"16","author":"Yan","year":"2025","journal-title":"Aging Dis"},{"key":"10.1016\/j.ejphar.2025.177857_bib84","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1093\/jn\/nxy065","article-title":"The citrulline recycling pathway sustains cardiovascular function in arginine-depleted healthy mice, but cannot sustain nitric oxide production during Endotoxin challenge","volume":"148","author":"Yuan","year":"2018","journal-title":"J. Nutr."},{"key":"10.1016\/j.ejphar.2025.177857_bib85","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jphs.2015.09.002","article-title":"Vascular nitric oxide: beyond eNOS","volume":"129","author":"Zhao","year":"2015","journal-title":"J. Pharmacol. Sci."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925006119?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925006119?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:29:59Z","timestamp":1778876999000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925006119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":85,"alternative-id":["S0014299925006119"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.177857","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Functional studies and molecular dynamics reveal BPP-BrachyNH2-induced relaxation in male rat small mesenteric arteries via binding to argininosuccinate synthase","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.177857","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"177857"}}