Skip to main content

Urinary adenosine triphosphate and nitric oxide levels in patients with underactive bladder: a preliminary study



Various in vitro and in vivo animal studies have shown that adenosine triphosphate (ATP) has a stimulatory role and nitric oxide (NO) has an inhibitory role in modulating bladder contractility. However, it is not known what happens to the urinary levels of ATP and NO in humans with underactive bladder (UAB).


In this prospective case–control study, we compared ATP and NO levels in twenty six male patients of UAB with a bladder contractility index (BCI) of < 100 and 18 healthy male volunteers without any lower urinary tract symptoms (LUTS).


The mean urinary ATP levels were significantly lower in cases compared to controls (546.1 ± 37.3 pg/µl vs. 610.7 ± 24.9 pg/µl, p value < 0.001) and the mean NO levels were significantly higher in cases compared to controls (1233.4 ± 91.2 pg/µl vs. 1126.3 ± 91.3.4 pg/µl, p value < 0.001). The mean NO/ATP ratio in cases was significantly higher than that of controls (2.26 ± 0.2 vs. 1.84 ± 0.18, p value < 0.000). Using receiver operating curve (ROC) analysis, we noted the area under the curve (AUC) for NO/ATP ratio to be 0.91 in the diagnosis of cases. A cut-off value of 2.06 for NO/ATP ratio had sensitivity, specificity and diagnostic accuracy of 88.5%, 88.9% and 88.6%, respectively, in diagnosing patients with UAB.


Patients with UAB have significantly higher levels of urinary NO and decreased levels of urinary ATP. Urinary NO/ATP levels can be considered as a noninvasive alternate test for diagnosing bladder underactivity.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

Data availability statement

The authors confirm that data supporting the findings of this study are available within the article/supplementary materials.


  1. 1.

    Osman NI, Chapple CR, Abrams P et al (2014) Detrusor underactivity and the underactive bladder: a new clinical entity? A review of current terminology, definitions, epidemiology, aetiology, and diagnosis. Eur Urol 65:389–398

    Article  Google Scholar 

  2. 2.

    Birder LA (2006) Urinary bladder urothelium: molecular sensors of chemical/thermal/mechanical stimuli. Vascul Pharmacol 45:221–226

    CAS  Article  Google Scholar 

  3. 3.

    Munoz A, Smith CP, Boone TB et al (2011) Overactive and underactive bladder dysfunction is reflected by alterations in urothelial ATP and NO release. Neurochem Int 58:295–300

    CAS  Article  Google Scholar 

  4. 4.

    Jeong SJ, Kim HJ, Lee YJ et al (2012) Prevalence and clinical features of detrusor underactivity among elderly with lower urinary tract symptoms: a comparison between men and women. Korean J Urol 53:342–348

    Article  Google Scholar 

  5. 5.

    Kumar V, Chapple CC, Chess-Williams R (2004) Characteristics of adenosine triphosphate [corrected] release from porcine and human normal bladder. J Urol 172:744–747

    CAS  Article  Google Scholar 

  6. 6.

    Harvey RA, Skennerton DE, Newgreen D et al (2002) The contractile potency of adenosine triphosphate and ecto-adenosine triphosphatase activity in guinea pig detrusor and detrusor from patients with a stable, unstable or obstructed bladder. J Urol 168:1235–1239

    CAS  Article  Google Scholar 

  7. 7.

    Birder LA, Nakamura Y, Kiss S et al (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860

    CAS  Article  Google Scholar 

  8. 8.

    Pandita RK, Andersson KE (2002) Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats. J Urol 168:1230–1234

    CAS  Article  Google Scholar 

  9. 9.

    Smith CP, Gangitano DA, Munoz A et al (2008) Botulinum toxin type A normalizes alterations in urothelial ATP and NO release induced by chronic spinal cord injury. Neurochem Int 52:1068–1075

    CAS  Article  Google Scholar 

  10. 10.

    Ozawa H, Chancellor MB, Jung SY et al (1999) Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis. J Urol 162:2211–2216

    CAS  Article  Google Scholar 

  11. 11.

    Cho KJ, Koh JS, Choi J et al (2017) Changes in adenosine triphosphate and nitric oxide in the urothelium of patients with benign prostatic hyperplasia and detrusor underactivity. J Urol 198:1392–1396

    CAS  Article  Google Scholar 

  12. 12.

    Daneshgari F, Liu G, Imrey PB (2006) Time dependent changes in diabetic cystopathy in rats include compensated and decompensated bladder function. J Urol 176:380–386

    Article  Google Scholar 

Download references


None to declare.

Author information




All authors have read and approved the final manuscript. AKG: protocol development, data collection and management, data analysis and manuscript writing. GS: data collection and management, data analysis and manuscript writing. SKD: data collection and management, data analysis, and manuscript writing. DZ: data collection and management, manuscript writing and editing. RSM: data collection and management, manuscript writing and editing. AKM: data collection and management, manuscript editing. APS: manuscript writing and editing. GSB: manuscript writing and editing.

Corresponding author

Correspondence to S. K. Devana.

Ethics declarations

Ethical approval

Received before study initiation(INT/IEC/2017/1396).

Consent to participate and publication

Obtained from all the patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Krishnan, A., Sharma, G., Devana, S.K. et al. Urinary adenosine triphosphate and nitric oxide levels in patients with underactive bladder: a preliminary study. World J Urol 39, 4421–4425 (2021).

Download citation


  • Underactive bladder
  • Adenosine triphosphate
  • Nitric oxide
  • Biomarker