Influence of losartan and enalapril on the diclofenac effect on leukocyte–endothelium interaction in spontaneously hypertensive rats (SHR)

Objectives

To investigate the influence of antihypertensives on the nonsteroidal anti-inflammatory drug effect on leukocyte–endothelium interaction in SHR, we tested losartan (L) or enalapril (E) and diclofenac (D) alone or in association (D+L or D+E).

Methods

The number of rollers, adherent and migrated leukocytes after stimulus with tumor necrosis factor alpha were determined in venules of the spermatic fascia of anesthetized SHR using intravital microscopy. We determined the venular diameter and the venular wall shear rate using an optical Doppler velocimeter, the number of circulating leukocytes, L-selectin or CD11/CD18 integrin expression on granulocytes by flow cytometry, and the intracellular adhesion molecule-1 (ICAM-1) or P-selectin expression in endothelial cells by imunohistochemistry. The left carotid artery of each anesthetized SHR was catheterized and the mean arterial blood pressure (MAP) was measured. The tail-cuff blood pressure (TBP) was measured in unanesthetized SHR.

Results

E and L reduced TBP and MAP, whereas D increased the TBP and MAP levels. The association of D did not interfere with the TBP and MAP lowering effect of E and L. The number of rollers was reduced by D, by L and by D + L. E and D + E did not modify the number of rollers. The number of adherent and migrated leukocytes was reduced by all treatments. Neither treatment increased the venular wall shear rate or modified the venular diameter, circulating leukocytes and L-selectin or CD11/CD18 integrin expression. All treatments decreased ICAM-1 expression. P-selectin expression was reduced by D, by L and by D + L, but E and D + E did not modify the P-selectin expression (Table 1).

Table 1

Conclusion

Our data allow us to suggest that the association of D did not interfere with the antihypertensive effect of E and L, but E interfered with the anti-inflammatory effect of D on leukocyte rolling and P-selectin expression. The reduction in ICAM-1 expression is involved and might explain the reduction of the number of adherent and migrated leukocytes observed.