Nitric oxide synthase induction with renal transplant rejection or infection

Abstract

Nitric oxide (NO) is readily oxidized to nitrate and nitrite and NO activates guanylyl cyclase, increasing cyclic GMP levels. To determine if nitric oxide synthase (NOS) is present in urine collected daily from patients following renal transplantation, we evaluated NOS activity in the leukocyte-rich particulate fraction and measured nitrate, nitrite, and cyclic GMP levels in the supernatant fraction of the urine. Reverse transcriptase-PCR and cDNA sequencing confirmed the presence of inducible NOS (iNOS) in cells obtained from the urine of renal transplant 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 citrulline/min/mg protein), when compared to post-renal transplantation patients without rejection or urinary tract infection (0.51 +/- 0.21 pmol citrulline/min/mg protein). Nitrate levels increased in renal transplant patients with rejection and nitrite levels increased in renal transplant patients with urinary tract infection (UTI). Cyclic GMP levels increased with both rejection and UTI. This study demonstrates the presence of NOS activity and inducible NOS-mRNA in cells isolated from the urine of patients undergoing renal allograft rejection.

Nitric oxide in patients with transitional bladder cancer

“…In several disease processes that affect the urinary tract, changes in iNOS activity have been identified. For example, in both urinary infection and renal transplant rejection, iNOS activity is increased [7,8]. In patients with interstitial cystitis, particulate NOS activity in the urine is decreased compared with controls [25].…”

“…iNOS is elevated during disease processes in the urinary tract [7,8]. It has been reported that NO production may be involved in the association between inflammation and human malignancies, including bladder cancer [9].…”

Expression of Inducible and Endothelial Nitric Oxide Synthases, Formation of Peroxynitrite and Reactive Oxygen Species in Human Chronic Renal Transplant Failure

“…In humans, conflicting data on NO x levels in both serum and urine have been found in acute renal allograft rejection (15)(16)(17)(18). Using immunohistochemistry, we recently found an increase in interstitial and glomerular iNOS expression and a decrease in glomerular eNOS expression in patients with AR compared with control kidneys (17).…”

“…Measurements of the stable end-products nitrite and nitrate (NO x ) suggest a role for NO¡ in acute rejection (AR) (15,16). In humans, conflicting data on NO x levels in both serum and urine have been found in acute renal allograft rejection (15)(16)(17)(18).…”

Nitrite and nitrate measurement in human urine by capillary electrophoresis

“…In the urinary bladder, NO formation is increased severalfold in bladder inflammatory conditions such as infectious, interstitial and irradiation cystitis [9,10]. Increase in urinary nitrate indicates systemic formation of NO in connection with diseases, such as infective gastroenteritis, or under conditions such as cardiac and renal allograft rejections [11][12][13]. Urinary nitrite, on the other hand, is the major end product of local NO formation in the urinary tract since there are no known mechanisms for nitrite conversion into nitrate in the urinary tract [14].…”