{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:28:05Z","timestamp":1781645285378,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T00:00:00Z","timestamp":1433289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2015,10]]},"abstract":"\n Objective<\/jats:title>\n \n To characterise the relaxation induced by the soluble guanylate cyclase (\n sGC<\/jats:styled-content>\n ) activator,\n BAY<\/jats:styled-content>\n 60\u20102770 (4\u2010({(4\u2010carboxybutyl) [2\u2010 (5\u2010fluoro\u20102\u2010{[4\u2032\u2010(trifluoromethyl) biphenyl\u20104\u2010yl]methoxy}phenyl)ethyl] amino}methyl)benzoic acid) in rabbit corpus cavernosum (\n CC<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Material and Methods<\/jats:title>\n \n The penis from male New Zealand rabbits was removed and fours strips of\n CC<\/jats:styled-content>\n were obtained. Concentration\u2013response curves to\n BAY<\/jats:styled-content>\n 60\u20102770 were constructed in the absence and presence of inhibitors of nitric oxide synthase, N (G)\u2010nitro\u2010L\u2010 arginine methyl ester (L\u2010\n NAME<\/jats:styled-content>\n , 100\u00a0\u03bc\n m<\/jats:sc>\n ),\n sGC<\/jats:styled-content>\n , 1H\u2010[1,2,4]oxadiazolo[4,3\u2010a]quinoxalin\u20101\u2010one (\n ODQ<\/jats:styled-content>\n , 10\u00a0\u03bc\n m<\/jats:sc>\n ) and phosphodiesterase type 5 (\n PDE<\/jats:styled-content>\n \u20105), tadalafil (0.1\u00a0\u03bc\n m<\/jats:sc>\n ). The potency (\n pEC<\/jats:styled-content>\n 50<\/jats:sub>\n ) and maximal response (\n E<\/jats:italic>\n max<\/jats:sub>\n ) values were determined. Then, electrical\u2010field stimulation (\n EFS<\/jats:styled-content>\n )\u2010induced contraction or relaxation was tested in the absence and presence of\n BAY<\/jats:styled-content>\n 60\u20102770 (0.1 or 1\u00a0\u03bc\n m<\/jats:sc>\n ) alone or combined with\n ODQ<\/jats:styled-content>\n (10\u00a0\u03bc\n m<\/jats:sc>\n ). For\n EFS<\/jats:styled-content>\n \u2010induced relaxation two protocols were used: (i)\n ODQ<\/jats:styled-content>\n (10\u00a0\u03bc\n m<\/jats:sc>\n ) was first incubated for 20\u00a0min and then\n BAY<\/jats:styled-content>\n 60\u20102770 (1\u00a0\u03bc\n m<\/jats:sc>\n ) was added for another 20\u00a0min (\n ODQ<\/jats:styled-content>\n +\n BAY<\/jats:styled-content>\n 60\u20102770); (ii) in different\n CC<\/jats:styled-content>\n strips,\n BAY<\/jats:styled-content>\n 60\u20102770 was incubated for 20\u00a0min followed by another 20\u00a0min with\n ODQ<\/jats:styled-content>\n (\n BAY<\/jats:styled-content>\n 60\u20102770 +\n ODQ<\/jats:styled-content>\n ). The intracellular levels of cyclic guanosine monophosphate (\n cGMP<\/jats:styled-content>\n ) were also determined.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n BAY<\/jats:styled-content>\n 60\u20102770 potently relaxed rabbit\n CC<\/jats:styled-content>\n with mean (\n sem<\/jats:sc>\n )\n pEC<\/jats:styled-content>\n 50<\/jats:sub>\n and\n E<\/jats:italic>\n max<\/jats:sub>\n values of 7.58 (0.19) and 81 (4)%, respectively. The inhibitors\n ODQ<\/jats:styled-content>\n (\n n<\/jats:italic>\n = 7) or tadalafil (\n n<\/jats:italic>\n = 7) produced 4.2\u2010 and 6.3\u2010leftward shifts, respectively in\n BAY<\/jats:styled-content>\n 60\u20102770\u2010induced relaxation without interfering with the\n E<\/jats:italic>\n max<\/jats:sub>\n values. The intracellular levels of\n cGMP<\/jats:styled-content>\n were augmented after stimulation with\n BAY<\/jats:styled-content>\n 60\u20102770 (1\u00a0\u03bc\n m<\/jats:sc>\n ) alone, whereas its co\u2010incubation with\n ODQ<\/jats:styled-content>\n produced even higher levels of\n cGMP<\/jats:styled-content>\n . The\n EFS<\/jats:styled-content>\n \u2010induced contraction was reduced in the presence of\n BAY<\/jats:styled-content>\n 60\u20102770 (1\u00a0\u03bc\n m<\/jats:sc>\n ) and this inhibition was even greater when\n BAY<\/jats:styled-content>\n 60\u20102770 was co\u2010incubated with\n ODQ<\/jats:styled-content>\n . The nitrergic stimulation induced\n CC<\/jats:styled-content>\n relaxation, which was abolished in the presence of\n ODQ<\/jats:styled-content>\n .\n BAY<\/jats:styled-content>\n 60\u20102770 alone increased the amplitude of relaxation. Co\u2010incubation of\n ODQ<\/jats:styled-content>\n and\n BAY<\/jats:styled-content>\n 60\u20102770 did not alter the relaxation in comparison with\n ODQ<\/jats:styled-content>\n alone. Interestingly, when\n BAY<\/jats:styled-content>\n 60\u20102770 was incubated before\n ODQ<\/jats:styled-content>\n ,\n EFS<\/jats:styled-content>\n \u2010induced relaxation was partly restored in comparison with\n ODQ<\/jats:styled-content>\n alone or\n ODQ<\/jats:styled-content>\n +\n BAY<\/jats:styled-content>\n 60\u20102770.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The relaxation induced by the\n sGC<\/jats:styled-content>\n activator,\n BAY<\/jats:styled-content>\n 60\u20102770 was increased after\n sGC<\/jats:styled-content>\n oxidation and unaltered in the absence of nitric oxide. Thus, this class of substances may have advantages over\n sGC<\/jats:styled-content>\n stimulators or\n PDE<\/jats:styled-content>\n \u20105 inhibitors for treating patients with erectile dysfunction and extensive endothelial damage.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.13105","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T02:06:17Z","timestamp":1424916377000},"page":"657-664","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Pharmacological characterisation of the relaxation induced by the soluble guanylate cyclase activator,\n BAY<\/scp>\n 60\u20102770 in rabbit corpus cavernosum"],"prefix":"10.1111","volume":"116","author":[{"given":"Camila S.","family":"Estancial","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Medical Sciences State University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata L.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medical Sciences State University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"De Nucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medical Sciences State University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Antunes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medical Sciences State University of Campinas (UNICAMP) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola Z.","family":"M\u00f3nica","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medical Sciences State University of Campinas 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