Effects of kinin B(1) and B(2) receptor antagonists on overactive urinary bladder syndrome induced by spinal cord injury in rats

Br J Pharmacol. 2012 Dec;167(8):1737-52. doi: 10.1111/j.1476-5381.2012.02127.x.


Background and purpose: Kinin B(1) and B(2) receptors have been implicated in physiological and pathological conditions of the urinary bladder. However, their role in overactive urinary bladder (OAB) syndrome following spinal cord injury (SCI) remains elusive.

Experimental approach: We investigated the role of kinin B(1) and B(2) receptors in OAB after SCI in rats.

Key results: SCI was associated with a marked inflammatory response and functional changes in the urinary bladder. SCI resulted in an up-regulation of B(1) receptor mRNA in the urinary bladder, dorsal root ganglion and spinal cord, as well as in B(1) protein in the urinary bladder and B(1) and B(2) receptor protein in spinal cord. Interestingly, both B(1) and B(2) protein expression were similarly distributed in detrusor muscle and urothelium of animals with SCI. In vitro stimulation of urinary bladder with the selective B(1) or B(2) agonist elicited a higher concentration-response curve in the SCI urinary bladder than in naive or sham urinary bladders. Cystometry revealed that treatment of SCI animals with the B(2) selective antagonist icatibant reduced the amplitude and number of non-voiding contractions (NVCs). The B(1) antagonist des-Arg(9) -[Leu(8) ]-bradykinin reduced the number of NVCs while the non-peptide B(1) antagonist SSR240612 reduced the number of NVCs, the urinary bladder capacity and increased the voiding efficiency and voided volume.

Conclusions and implications: Taken together, these data show the important roles of B(1) and B(2) receptors in OAB following SCI in rats and suggest that blockade of these receptors could be a potential therapeutic target for controlling OAB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bradykinin B1 Receptor Antagonists
  • Bradykinin B2 Receptor Antagonists
  • Ganglia, Spinal / physiology
  • Male
  • Muscle Contraction
  • Rats
  • Rats, Wistar
  • Receptor, Bradykinin B1 / agonists
  • Receptor, Bradykinin B1 / physiology*
  • Receptor, Bradykinin B2 / agonists
  • Receptor, Bradykinin B2 / physiology*
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology*
  • Urinary Bladder / physiology
  • Urinary Bladder, Overactive / etiology
  • Urinary Bladder, Overactive / metabolism
  • Urinary Bladder, Overactive / physiopathology*


  • Bradykinin B1 Receptor Antagonists
  • Bradykinin B2 Receptor Antagonists
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2