Background. Although angiotensin II (Ang II) has inflammatory effects, little is known about its role in polymorphonuclear leucocytes (PMLs). To elucidate the role of Ang II in PMLs ROS production, we examined hydrogen peroxide (H2O2), one of the ROS, and NO production in AT1a receptor knockout (AT1KO) mice. Methods and Results. PMLs were analyzed from Ang II type 1a receptor knockout mice (AT1KO) and C57BL/6 wild type mice. Using flow cytometry, we studied hydrogen peroxide (H2O2) production from PMLs after Staphylococcus aureus phagocytosis or phorbol myristate acetate (PMA) stimulation. Nitric oxide (NO) production in the AT1KO was low at basal and after phagocytosis. In the AT1KO, basal H2O2 production was low. After PMA or phagocytosis stimulation, however, H2O2 production was comparable to wild type mice. Next we studied the H2O2 production in C57BL/6 mice exposed to Ang II or saline. H2O2 production stimulated by PMA or phagocytosis did not differ between the two groups. Conclusions. AT1a pathway is not necessary for PMLs H2O2 production but for NO production. There was a compensatory pathway for H2O2 production other than the AT1a receptor. 1. Introduction Although angiotensin (Ang) II has been reported to have proinflammatory and oxidative effects, little is known about the correlation between Ang II and reactive oxygen species (ROS) in polymorphonuclear leukocytes (PMLs). Activation of the renin-angiotensin system and increased production of Ang II are implicated in the pathogenesis of hypertension, atherosclerosis, and cardiac hypertrophy [1]. Ang II acts through high-affinity cell surface receptors, which are linked to pathways classically associated with G-protein-coupled and tyrosine-kinase-mediated responses [2]. Ang II type 1 (AT1) receptors for Ang II have also been found in circulating neutrophils [3] and human circulating PMLs [4]; furthermore, Ang II-induced cell activation has been reported [5, 6]. One major mechanism through which Ang II induces pathological effects is regulated by the generation of superoxide and other ROS [7]. ROS generation is mediated through the activation of NADPH oxidase in PMLs. PMLs ROS production participates in host defense by killing bacteria, but can also damage host tissues and play an important role in disease pathogenesis. Nitric oxide (NO) regulates important functions of PMLs, including chemotaxis, adhesion, aggregation, apoptosis, and PMN-mediated bacterial killing or tissue damage [8]. It has been reported that rat PMLs constitutively express neural NO synthase (nNOS) mRNA and nNOS protein and
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