URINARY TRACT INFLAMMATION--ROLE OF NITRIC OXIDE

Yale University, New Haven CT

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Abstract

Nitric oxide is a ubiquitous-messenger molecule that can exert proinflammatory, bacteriocidal, and anti-viral actions. Difficulty was found in identifying inducible-nitric oxide synthase (iNS) in humans, but we identified in iNOS in human urinary leukocytes during urinary tract infection, kidney transplant rejection, and bladder cancer. With interstitial cystititis, iNOS activity was decreased compared to iNOS activity from health controls. The specific aim of this research is to clarify the activators of nitri oxide synthase and the effect that nitric oxide synthase has on leukocytes during disease processes. The mechanism of cellular recruitment into urine with increased and/or decreased NOS activity remains to be investigated. By enzyme activity measurements, by RNA and cDNA evaluation, b immunohistochemistry, and by western blot, NOS and its effectors will be evaluated over time. Also, the interplay between NO and cellular growth and death, interleukins, L-arginine, NADPH-diaphorase, and endothelial-1 will be identified. Assessing NOS during urinary tract infection, urinary tumors, renal transplantation, and interstitial cystitis will aid in understanding No's role in cellular defense and in developing diagnosis and treatment protocols concerning urinary tract disease.