Bradykinin increases BP in endotoxemic rat: functional and biochemical evidence of angiotensin II AT1 /bradykinin B2 receptor heterodimerization.
Br J Pharmacol
; 176(14): 2608-2626, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30945263
BACKGROUND AND PURPOSE: Bradykinin may induce vasoconstriction in selected vessels or under specific experimental conditions. We hypothesized that inflammatory stimuli, such as endotoxin challenge, may induce the dimerization of AT1 /B2 receptors, altering the vascular effects of bradykinin. EXPERIMENTAL APPROACH: Wistar rats received LPS (1 mg·kg-1 , i.p.) and were anaesthetized for assessment of BP. Mesenteric resistance arteries were used in organ baths and subjected to co-immunoprecipitation and Western blot analyses. KEY RESULTS: At 24 and 48 hr after LPS, bradykinin-induced hypotension was followed by a sustained increase in BP, which was not found in non-endotoxemic animals. The B2 receptor antagonist Hoe-140 fully blocked the responses to bradykinin. The pressor effect of bradykinin was not prevented by prazosin, an α1 -adrenoceptor antagonist, but it was inhibited by the AT1 receptor antagonist losartan or the Rho-kinase inhibitor Y-27632. Endotoxemic rats also displayed enhanced pressor responses to angiotensin II, which were blocked by Hoe-140. Co-immunoprecipitation isolated using anti-B2 or anti-AT1 receptor antibodies showed that resistance arteries presented augmented levels of the AT1 /B2 receptor complexes at 24 hr after LPS injection. The presence of AT1 /B2 receptor heterodimers did correlate with the development of losartan-sensitive contractile responses to bradykinin and potentiation of angiotensin II-induced contraction, which was prevented by Hoe-140. CONCLUSIONS AND IMPLICATIONS: Endotoxin challenge is a stimulus for AT1 /B2 receptor heterodimerization in native vessels and shifts the B2 receptor-dependent vascular effect of bradykinin to a more complex pathway, which also depends on AT1 receptors and their intracellular signalling pathways.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatadores
/
Pressão Sanguínea
/
Bradicinina
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Receptor Tipo 1 de Angiotensina
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Receptor B2 da Bradicinina
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido