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Microcirculation ; 24(8)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28857417

RESUMO

OBJECTIVE: Previously, we found that diet-induced HHcy in mice caused decreased eNOS expression and signaling in mesenteric arteries, but greatly enhanced non-NOS, non-prostacyclin-dependent vasodilation, which involves MEJ communication. To further assess whether HHcy enhances MEJ communication, this study examined endothelium-dependent attenuation of phenylephrine-induced vasoconstriction (myoendothelial feedback) and key molecules involved. METHODS: Myoendothelial feedback was examined in isolated mouse mesenteric arteries, after 6-weeks diet-induced HHcy, using pressure myography. Gap junction (Cx37, Cx40, Cx43), NOS (eNOS, nNOS, iNOS), and potassium channel (IK1) protein expression were measured with immunoblots, and connexin mRNAs with real-time PCR. Contribution of nNOS + iNOS to vasomotor responses was assessed using the drug TRIM. RESULTS: Myoendothelial feedback was significantly (P < .05) enhanced in HHcy arteries compared to control, coincident with significantly greater Cx37 and IK1 protein and Cx37 mRNA. Cx43 protein, but not mRNA, was significantly less in HHcy, and Cx40 was not different. eNOS protein was significantly less in HHcy. nNOS and iNOS were not different. TRIM had little effect on vasomotor function. CONCLUSIONS: Diet-induced HHcy enhanced myoendothelial feedback, and increased Cx37 and IK1 expression may contribute. nNOS or iNOS did not upregulate to compensate for decreased eNOS, and they had little involvement in vasomotor function.


Assuntos
Conexinas/metabolismo , Junções Comunicantes/metabolismo , Regulação da Expressão Gênica , Hiper-Homocisteinemia/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/biossíntese , Artérias Mesentéricas/metabolismo , Animais , Alimentos Formulados/efeitos adversos , Junções Comunicantes/patologia , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/patologia , Hiper-Homocisteinemia/fisiopatologia , Masculino , Artérias Mesentéricas/patologia , Artérias Mesentéricas/fisiopatologia , Camundongos , Óxido Nítrico Sintase Tipo I/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo III/biossíntese , Proteína alfa-4 de Junções Comunicantes
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