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We hypothesized that inflammatory stimuli, such as endotoxin challenge, may induce the dimerization of AT<jats:sub>1<\/jats:sub>\/B<jats:sub>2<\/jats:sub> receptors, altering the vascular effects of bradykinin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Wistar rats received LPS (1\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.p.) and were anaesthetized for assessment of BP. Mesenteric resistance arteries were used in organ baths and subjected to co\u2010immunoprecipitation and Western blot analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>At 24 and 48\u00a0hr after LPS, bradykinin\u2010induced hypotension was followed by a sustained increase in BP, which was not found in non\u2010endotoxemic animals. The B<jats:sub>2<\/jats:sub> receptor antagonist Hoe\u2010140 fully blocked the responses to bradykinin. The pressor effect of bradykinin was not prevented by prazosin, an \u03b1<jats:sub>1<\/jats:sub>\u2010adrenoceptor antagonist, but it was inhibited by the AT<jats:sub>1<\/jats:sub> receptor antagonist losartan or the Rho\u2010kinase inhibitor Y\u201027632. Endotoxemic rats also displayed enhanced pressor responses to angiotensin II, which were blocked by Hoe\u2010140. Co\u2010immunoprecipitation isolated using anti\u2010B<jats:sub>2<\/jats:sub> or anti\u2010AT<jats:sub>1<\/jats:sub> receptor antibodies showed that resistance arteries presented augmented levels of the AT<jats:sub>1<\/jats:sub>\/B<jats:sub>2<\/jats:sub> receptor complexes at 24\u00a0hr after LPS injection. The presence of AT<jats:sub>1<\/jats:sub>\/B<jats:sub>2<\/jats:sub> receptor heterodimers did correlate with the development of losartan\u2010sensitive contractile responses to bradykinin and potentiation of angiotensin II\u2010induced contraction, which was prevented by Hoe\u2010140.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Endotoxin challenge is a stimulus for AT<jats:sub>1<\/jats:sub>\/B<jats:sub>2<\/jats:sub> receptor heterodimerization in native vessels and shifts the B<jats:sub>2<\/jats:sub> receptor\u2010dependent vascular effect of bradykinin to a more complex pathway, which also depends on AT<jats:sub>1<\/jats:sub> receptors and their intracellular signalling pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14685","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T01:30:00Z","timestamp":1554341400000},"page":"2608-2626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Bradykinin increases BP in endotoxemic rat: functional and biochemical evidence of angiotensin II AT<sub>1<\/sub>\/bradykinin B<sub>2<\/sub> receptor heterodimerization"],"prefix":"10.1111","volume":"176","author":[{"given":"Elaine Leoc\u00e1dia","family":"Anton","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Laboratory of Cardiovascular Biology Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Cardiovascular Biology Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-1569","authenticated-orcid":false,"given":"Jamil","family":"Assreuy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Cardiovascular Biology Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-226X","authenticated-orcid":false,"given":"Jos\u00e9 Eduardo","family":"da Silva\u2010Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Laboratory of Cardiovascular Biology Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:26:2-3:185"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0901-1003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35024095"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3182336a34"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.07.020"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.18.6374"},{"key":"e_1_2_11_10_1","first-page":"902","article-title":"Mechanisms involved in the contractile responses of kinins in rat portal vein rings: Mediation by B1 and B2 receptors","volume":"268","author":"Campos A. 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