Angiotensin II regulatesthe radical production of polymorphonuclearleukocytes: Evidence in Angiotensi II type 1a receptor knockout mice

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Objective Although angiotensin II (AII) has been linked to its inflammatory and oxidative effects on cytokine or chemokine, little is known about the phagocytic function of AII on polymorphonuclear leulocytes (PMN). We evaluate the role of AII in reactive oxygen species (ROS) and of nitric oxide (NO). Methods Using flow cytometry, we compared the ROS production of PMN after (propidium iodide-labeled) S. aureus or phorbol myristate acetate (PMA) (25 μg/ml). We tested the PMN from the 5 groups: C57BL/6 wild type mice (Group C), AII type 1A receptor knock-out mice (Group KO), C57BL/6 mice exposed to either AII (1000 ng/kg per minute subcutaneously) (Group A) or saline (Group S) for 2 weeks, and C57BL/6 mice administrated AII receptor blocker, losartan (100mg/L drinking water) for 2 weeks (Group L). Animals did not differ in body weight or PMN counts. Results ROS production stimulated by PMA was higher in the group A than in other groups. ROS production stimulated by phagocytosis was also higher in the group A than in group C. ROS production at basal in group KO was lower than other groups. In the group KO, NO production both at basal and phagocytic stimulation was lower than in other groups. The radical production stimulated by PMA or phagocytosis was observed even in the Group KO. Conclusions Ang II stimulated the ROS production of PLM both by phagocytosis and PMA stimulation. Under the chronic stimulation with Ang II, NO production was not changed after the stimulation of phagocytosis.