NITRIC-OXIDE SYNTHASE INDUCTION WITH RENAL-TRANSPLANT REJECTION OR INFECTION

Nitric oxide (NO) is readily oxidized to nitrate and nitrite and NO ac tivates guanylyl cyclase, increasing cyclic GMP levels. To determine i f nitric oxide synthase (NOS) is present in urine collected daily from patients following renal transplantation, we evaluated NOS activity i n the leukocyte-rich particulate fraction and measured nitrate, nitrit e, and cyclic GMP levels in the supernatant fraction of the urine. Rev erse transcriptase-PCR and cDNA sequencing confirmed the presence of i nducible NOS (iNOS) in cells obtained from the urine of renal transpla nt patients with rejection. NOS activity was elevated significantly in renal transplant patients with rejection (6.40+/-1.47 pmol citrulline /min/mg protein) or with urinary tract infection (29.56+/-11.00 pmol c itrulline/min/mg protein), when compared to post-renal transplantation patients without rejection or urinary tract infection (0.51+/-0.21 pm ol citrulline/min/mg protein). Nitrate levels increased in renal trans plant patients with rejection and nitrite levels increased in renal tr ansplant patients with urinary tract infection (UTI). Cyclic GMP level s increased with both rejection and UTI. This study demonstrates the p resence of NOS activity and inducible NOS-mRNA in cells isolated from the urine of patients undergoing renal allograft rejection.