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−1·d−1, 15 d) alone or combined with amlodipine (10 mg·kg−1·d−1, 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.
From the Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Received for publication September 19, 2007; accepted February 7, 2008.
The authors are grateful to FAPESP and PRONEX by supporting this work. Stephen Fernandes Rodrigues is recipient of a scholarship from FAPESP.
The authors report no conflicts of interest.
Correspondence: Zuleica Bruno Fortes, PhD, Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo. 05508-900, Av. Prof. Lineu Prestes, 1524 - São Paulo, SP, Brazil (e-mail: email@example.com).