NITRIC OXIDE IN DEFENSE OF PERITONEAL CAVITY AGAINST MICROBIAL PATHOGENS--CAPD

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Nitric oxide (NO) and its metabolite peroxinitrite have recently emerged as principal secretory products of activated macrophages and elicited polymorphonuclear cells in providing the defense against a broad range of microorganisms. The role of these metabolic products in patients on CAPD and in those with acute peritonitis awaits elucidation. Theoretically, an excessive production of NO may be deleterious to the mesothelial cells of the peritoneal cavity., whereas its deficiency may underscore the predilection to infection. Preliminary data demonstrates that the majority of patients with acute bacterial peritonitis have increased NO production. The recovery from peritonitis is associated with the decline in NO generation. We put forward a hypothesis that deficient production of nitric oxide may be responsible for the defective defense barrier and persistence of bacterial infection which occurs in patients with frequent, recurring peritonitis. This hypothesis will be tested in longitudinal and cross-sectional studies of CAPD patients. The concentration of nitrite, L- arginine and ADMA will be determined at specified interval during chronic treatment and during the course of peritonitis. The data will be analyzed with reference to the frequency of infections, success of therapy, and other clinical parameters. We anticipate to circumscribe a subgroup of patients with impairment in L-arginine metabolism-these patients may benefit from therapeutic correction of L-arginine metabolism.