Amlodipine reduces the antimigratory effect of diclofenac in spontaneously hypertensive rats.
Amlodipine, an antihypertensive drug, and diclofenac, an antiinflammatory drug, may generally be combined, particularly in elderly patients; therefore, the potential for their interaction is high. We aim to determine if amlodipine interferes with the antimigratory effect of diclofenac. For this, male spontaneously hypertensive rats (SHRs) were treated with either diclofenac (1 mg.kg.d, 15 d) alone or combined with amlodipine (10 mg.kg.d, 15 d). Leukocyte rolling, adherence, and migration were studied by intravital microscopy. Diclofenac did not change (180.0 +/- 2.3), whereas amlodipine combined (163.4 +/- 5.1) or not (156.3 +/- 4.3) with diclofenac reduced the blood pressure (BP) levels in SHR (183.1 +/- 4.4). Diclofenac and amlodipine reduced leukocyte adherence, migration, and ICAM-1 expression, whereas only diclofenac reduced rolling leukocytes as well. Combined with amlodipine, the effect of the diclofenac was reduced. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, P-selectin, PECAM-1, L-selectin, or CD-18 expressions. No difference could be found in plasma concentrations of both drugs given alone or in association. In conclusion, amlodipine reduces leukocyte migration in SHR, reducing endothelial cell ICAM-1 expression. Amlodipine reduces the effect of the diclofenac, possibly by the same mechanism. A pharmacokinetic interaction as well as an effect on the other adhesion molecules tested could be discarded.
Rodrigues
Stephen Fernandes
SF
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Dossantos
Rosangela Aparecida
RA
de Oliveira
Maria Aparecida
MA
Rastelli
Viviani Milan
VM
de Nucci
Gilberto
G
Tostes
Rita de Cássia
Rde C
Nigro
Dorothy
D
Carvalho
Maria Helena
MH
Fortes
Zuleica B
ZB
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D004008:Diclofenac / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D051381:Rats; D011918:Rats, Inbred SHR
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004008:Diclofenac; D017311:Amlodipine