The inhibitory effect of BKCa channels induced by autoantibodies against angiotensin II type 1 receptor is independent of AT1R.
Acta Biochim Biophys Sin (Shanghai)
; 50(6): 560-566, 2018 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-29697782
ABSTRACT
Autoantibodies against angiotensin II Type 1 receptor (AT1-AA) are routinely detected in the serum of preeclampsia patients, which results in an increase in vascular tone and an elevation in intracellular calcium concentration of rat vascular smooth muscle (VSM). The big conductance calcium-activated potassium channels (BKCa channels) account for the dominant outward currents in VSMCs, contributing to membrane hyperpolarization and vasodilation. In the present study, we investigated the effect of AT1-AA on BKCa channels. A preeclampsia model was established by passively immunizing healthy pregnant BALB/c mice with AT1-AA extracted from hybridoma culture supernatant. Blood pressure, serum AT1-AA levels, and urinary protein were measured in the immunized mice. BKCa channel expression was detected using qRT-PCR and immunohistochemical technique. The patch-clamp technique was used to record the single currents of BKCa channels in the HEK293T cells that had been transfected. AT1-AA immunized mice exhibited elevated AT1-AA and urinary protein levels compared with mice of the vehicle group. Systolic blood pressure was also increased in the immunized group. BKCa channel ß1-subunit expression was reduced in the mesenteric arteries of immunized mice. AT1-AA could inhibit the BKCa currents and the inhibitory effects were not completely reversed following the application of valsartan, an inhibitor of AT1 receptor. In conclusion, AT1-AA could decrease BKCa expression and inhibit BKCa activity independent of AT1R. These inhibitory effects are likely to be contributory factors in the promotion of increased vascular tone caused by AT1-AA in preeclampsia.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Ativação do Canal Iônico
/
Receptor Tipo 1 de Angiotensina
/
Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Acta Biochim Biophys Sin (Shanghai)
Assunto da revista:
BIOFISICA
/
BIOQUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China