Losartan Attenuates the Antimigratory Effect of Diclofenac in Spontaneously Hypertensive Rats
| Autor: | Maria Helena Catelli de Carvalho, L L Martinez, Ana Silvia Miguel, Rita C. Tostes, Maria Aparecida Oliveira, Dorothy Nigro, Viviani Milan Ferreira Rastelli, Zuleica Bruno Fortes, José Walber Miranda Costa Cruz |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Leukocyte migration Diclofenac Blood Pressure CD18 Pharmacology Losartan Leukocyte Count Pharmacokinetics Rats Inbred SHR Cell Adhesion Leukocytes Animals Edema Medicine Drug Interactions Leukocyte Rolling Antihypertensive Agents Angiotensin II receptor type 1 Tumor Necrosis Factor-alpha business.industry Microcirculation Anti-Inflammatory Agents Non-Steroidal Flow Cytometry Immunohistochemistry Rats stomatognathic diseases Blood pressure Gastric Mucosa Hypertension cardiovascular system Cardiology and Cardiovascular Medicine business Intravital microscopy circulatory and respiratory physiology medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 46:190-199 |
| ISSN: | 0160-2446 |
| Popis: | Many patients with hypertension, particularly elderly patients, take nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensive agents. However, few studies describe the effect of the association of antihypertensive agents with NSAIDs on inflammatory response in hypertension. To investigate this, spontaneously hypertensive rats (SHRs) were treated with either diclofenac alone or diclofenac combined with losartan (an AT1 angiotensin II antagonist). The leukocyte-endothelial interaction was then observed using intravital microscopy. Blood pressure of SHR (169.6+/-3.6) was increased by diclofenac (186.4+/-2.9), reduced by losartan (152.6+/-3.5), and reduced by the combination of the 2 (158.9+/-3.7). All the treatments tested reduced the number of rollers, adherent and migrated leukocytes, and the expression of endothelial intercellular adhesion molecule-1 and P-selectin. The association of losartan reduced the effect of diclofenac on leukocyte migration. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, and L-selectin expression on granulocytes. The reduction of CD11/CD18 expression induced by diclofenac alone was hindered by losartan. A pharmacokinetic interference between losartan and diclofenac was ruled out since no significant differences were observed in the plasma concentrations of each drug when they were associated. In conclusion, although diclofenac does not interfere with the losartan antihypertensive effect, losartan attenuates the effect of diclofenac has on leukocyte behavior and expression of adhesion molecules. Losartan has an antimigratory effect, reducing leukocyte migration by reducing ICAM-1 and P-selectin expression. Losartan may hinder the full expression of the antimigratory effect of diclofenac. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|