RESUMO
The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.
Assuntos
Periodontite/imunologia , Periodontite/patologia , Periodonto/imunologia , Periodonto/patologia , Sistema Renina-Angiotensina , Adulto , Sequência de Aminoácidos , Angiotensina I/análise , Angiotensina I/imunologia , Angiotensina II/análise , Angiotensina II/imunologia , Animais , Células Cultivadas , Feminino , Gengiva/citologia , Gengiva/imunologia , Gengiva/patologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/imunologia , Ratos Wistar , Receptores de Angiotensina/análise , Receptores de Angiotensina/imunologia , Renina/imunologia , Adulto JovemRESUMO
The activity of a renin-like enzyme (RLE) previously found in rat copora lutea was studied during lactation. Luteal RLE concentration significantly increased after delivery and reached a maximum on day 5 of lactation. Plasmatic levels of PRL and progesterone also increased through lactation. Treatment with 2 bromo-alpha-ergocryptine, which diminished plasma PRL and progesterone levels, enhanced luteal RLE activity. Therefore, the increase in luteal RLE during lactation seems to be independent of PRL and progesterone levels, but dopamine could be involved in its regulation. The increase in luteal RLE is not related to the intensity of the suckling stimulus, since RLE values were not modified in mothers suckling 2 to 10 pups. In conclusion, RLE activity in rat corpora lutea changes during lactation with a pattern similar to that of plasmatic PRL and progesterone, but seems not to be regulated by these hormones, nor by the intensity of suckling. On the contrary, luteal RLE may be regulated by dopamine.
Assuntos
Ácido Aspártico Endopeptidases , Corpo Lúteo/metabolismo , Endopeptidases/metabolismo , Lactação/metabolismo , Animais , Formação de Anticorpos , Bromocriptina/farmacologia , Feminino , Gravidez , Progesterona/sangue , Prolactina/sangue , Ratos , Ratos Endogâmicos , Renina/imunologiaRESUMO
Specific high-titer antibodies to rat kidney renin were raised using pure rat kidney renin conjugated with tetanus toxoid as antigen. The titers of two antisera for 50% inhibition of rat kidney renin activity were 80 000 and 700 000, respectively. The antibody inhibited the enzyme activities of hog kidney renin and mouse submaxillary gland renin at concentrations 1 000 times higher than required for rat kidney renin but did not inhibit human renal renin or rat kidney cathepsin D. The antibody can be used for characterizing the physiological and pathophysiological role of renin in blood pressure regulation, for the histochemical localization of renin in rat tissues and for distinguishing specific renin activity from the nonspecific renin-like activity of cathepsin D.