Nitric oxide : a marker for inflammation in the lower urinary tract

The main aim of this work is to investigate the role of Nitric oxide (NO) as a diagnostic marker for inflammation in the lower urinary tract. NO exerts multiple modulating effects on inflammation and plays a key role in the regulation of immune responses. NO is formed enzymatically in vivo from Larginine by several NO synthases (NOS). Being a free radical, NO has a very short half live in biological systems. In contrast, NO in the gaseous phase is more stable, which makes it possible to measure NO in luminal structures such as the urinary bladder. We have developed a new method for measurement of luminal NO formation involving the insertion of a silicon catheter through the urethra. The balloon is filled with NOfree air, which is incubated in the urinary bladder for sampling of NO from the bladder or placed in the prostatic urethra for sampling of NO from the prostate.

We observed an almost 20-fold increase in urinary bladder concentration of NO in patients with interstitial cystitis (IC), compared with control subjects. The NO concentration in the urinary bladder of patients with detrusor instability, outflow obstruction and bladder hypersensitivity was as low as in the asymptomatic control subjects suggesting that measurement of NO in air from the urinary bladder can differentiate between inflammatory and non-inflammatory lower urinary tract conditions.

Patients with classic IC, who responded with a significant reduction in symptom score to cortisone treatment, also had a clear reduction in NO formation in the bladder in contrast to non-responders. There was also a significant correlation between changes in symptom score and NO formation in each individual patient. This implies that measurement of NO formation can be used also for evaluation of treatment response in lower urinary tract inflammatory disorders.

In patients with chronic abacterial prostatitis/chronic pelvic pain syndrome only 32% had an elevated NO concentration in the prostatic urethra. These patients also had more than 10 leukocytes in the expressed prostatic secretion, while none of the patients with no signs of inflammation in the prostatic secretion had an elevated NO- formation. Thus, NO may be used to differentiate between inflammatory and non-inflammatory chronic abacterial prostatitis.

The presence of inducible NOS and the NO formation was investigated in bladder cancer patients. We found increased NO formation in the urinary bladder in patients with Bacillus Calmette Guérin (BCG) treated bladder cancer and carcinoma in situ, suggesting that NO may be an important factor in bladder cancer biology and that the BCG effect in bladder cancer may be due to the stimulation of NO formation. In summary the use of NO as an objective marker may improve the diagnostics of lower urinary tract disorders.

List of scientific papers

I. Ehren I, Hosseini A, Lundberg JO, Wiklund NP (1999). "Nitric oxide: a useful gas in the detection of lower urinary tract inflammation. " J Urol 162(2): 327-9
https://pubmed.ncbi.nlm.nih.gov/10411031

II. Ehren I, Hosseini A, Herulf M, Lundberg JO, Wiklund NP (1999). "Measurement of luminal nitric oxide in bladder inflammation using a silicon balloon catheter: a novel minimally invasive method. " Urology 54(2): 264-7
https://pubmed.ncbi.nlm.nih.gov/10443722

III. Hosseini A, Ehrén I, Wiklund NP (2004). "Nitric oxide as an objective marker for evaluation of inflammation and treatment response in patients with classic intertitial cystitis." Journal of Urology (Submitted)

IV. Hosseini A, Herulf M, Ehrén I (2004). "Measurement of nitric oxide may differentiate between inflammatory and non-inflammatory prostatitis." Scandinavian Journal of Urology and Nephrology (Accepted)

V. Hosseini A, Renström Koskela L, Ehrén I, Aguilar Santelises M, Sirsjo A, Wiklund NP (2004). "Enhanced formation of nitric oxide in bladder carcinoma in situ and BCG treated bladder cancer." Journal of Urology (Submitted)