RESUMO
Because adrenergic contractions can contribute to the development of life-threatening spasm of coronary artery bypass graft, this study was performed to investigate the effect of adenosine 3-phosphate (ATP)-sensitive K channel (KATP) opener P1075 on contractions of isolated human saphenous vein (HSV) and human internal mammary artery (HIMA). Phasic contractions were evoked by electric field stimulation (20 Hz) and noradrenaline. The sustained contractions were evoked by phenylephrine. The presence of pore-forming Kir6.1 and Kir6.2 subunits of the KATP channels in the HIMA and only Kir6.2 in the HSV was confirmed immunomorphologically. P1075 inhibited in the HSV only, the electrical field stimulation contractions more strongly than noradrenaline contractions. In addition, the phenylephrine contractions of HSV were more sensitive to P1075 in comparison to those of HIMA. Glibenclamide, a KATP channel blocker antagonized the vasodilatation produced by P1075 in both grafts differently, because its effect was more prominent on the P1075-induced inhibition of contractions of HSV than of HIMA. We conclude that P1075 has a vasorelaxant effect and inhibited adrenergic contractions of the tested grafts. This effect is graft and vasoconstrictor selective and seems to be mediated by Kir6.1- and/or Kir6.2-containing KATP channels. Thus, P1075 can be considered as a potential drug in the prevention of graft spasm.
Assuntos
Guanidinas/farmacologia , Canais KATP/agonistas , Artéria Torácica Interna/efeitos dos fármacos , Piridinas/farmacologia , Veia Safena/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Idoso , Estimulação Elétrica , Glibureto/farmacologia , Guanidinas/antagonistas & inibidores , Humanos , Canais KATP/metabolismo , Masculino , Artéria Torácica Interna/citologia , Artéria Torácica Interna/metabolismo , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Especificidade de Órgãos , Concentração Osmolar , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Subunidades Proteicas/metabolismo , Piridinas/antagonistas & inibidores , Veia Safena/citologia , Veia Safena/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/antagonistas & inibidoresRESUMO
Neural cell adhesion molecule (NCAM) is important for cell migration and it could be expressed in some renal cell carcinoma (RCC). In recent decades, the incidence of RCC has been steadily rising by 2-4% each year. In this study NCAM expression and correlation with nuclear grade in different RCC were analyzed. We analyzed NCAM expression on 7 different RCC cell lines and 32 different RCC by immunohistochemistry, immunofluorescence, Western blot and FACS analysis. NCAM expression is detected in 6 cell lines and 16 RCC cases. NCAM-140 kDa isoform is expressed in different RCC and RCC cell lines. NCAM expression in non-invasive clear cell RCC is lower than in clear cell RCC with high nuclear grade. Expression of NCAM is not exclusive for specific RCC type, so NCAM can not be used as a specific diagnostic marker for RCC. NCAM expression is in correlation with nuclear grade in clear cell RCC, suggesting that NCAM expression is involved in aggressive behavior and metastatic potential in RCC.