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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2008.tde-10092008-122935
Document
Author
Full name
Stephen Fernandes de Paula Rodrigues
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Fortes, Zuleica Bruno (President)
Bendhack, Lusiane Maria
Chaves, Maria Luiza Morais Barreto de
Farsky, Sandra Helena Poliselli
Lima, Wothan Tavares de
Title in Portuguese
Interação anlodipina/diclofenaco sobre o comportamento leucocitário em ratos espontaneamente hipertensos (SHR) e ratos wistar normotensos.
Keywords in Portuguese
Anlodipina
Diclofenaco
Hipertensão
Interação de medicamentos
Interação leucócito-endotélio
SHR
Abstract in Portuguese
Anlodipina e diclofenaco podem ser combinados de forma que o potencial de interação é alto. Investigamos se anlodipina interfere com o efeito antimigratório do diclofenaco em ratos espontaneamente hipertensos (SHR) e ratos wistar. Os ratos foram tratados (15 dias) com diclofenaco e anlodipina, juntos ou separadamente. A migração leucocitária foi estudada por microscopia intravital e a expressão de moléculas de aderência por imunohistoquímica. A anlodipina reduziu migração leucocitária em SHR e ratos wistar por reduzir a expressão de ICAM-1 em células endoteliais venulares. A redução da migração leucocitária em ratos wistar pode decorrer também da redução da expressão de PECAM-1 em células endoteliais. A combinação reduziu o efeito do diclofenaco sobre a migração em SHR e wistar. Em SHR esse efeito envolveu a redução de ICAM-1. A redução da PA causada pela anlodipina em SHR parece contribuir para a redução da migração leucocitária. Interação farmacocinética foi excluída.
Title in English
Amlodipine and diclofenac interaction on leukocyte behavior in spontaneously hypertensive rats (SHR) and normotensive wistar rats.
Keywords in English
Amlodipine
Diclofenac
Drug interaction
Hypertension
Leukocyte-endothelial interaction
SHR
Abstract in English
Amlodipine and diclofenac may be combined so the potential for interaction of both is high. We determined if amlodipine interferes with the antimigratory effect of diclofenac in spontaneously hypertensive rats (SHR) and wistar rats. Rats were treated with either diclofenac or amlodipine alone or combined (for 15 days). Leukocyte migration was evaluated by intravital microscopy and cell adherence molecules expression by immunohistochemistry. Amlodipine reduces migration in both SHR and wistar rats by reducing venular endothelial cell ICAM-1 expression. In wistar the antimigratory effect of amlodipine may also be due to reduction in PECAM-1 expression. Diclofenac effect was reduced by amlodipine in both SHR and wistar. In SHR amlodipine reduces the effect of diclofenac by impairing its reducing effect on ICAM-1. Reduction of the BP levels seems to contribute to reduction of the leukocyte migration caused by amlodipine in SHR. Pharmacokinetic interaction was excluded.
 
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Publishing Date
2008-09-22
 
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