Effects of intrathecal administration of pituitary adenylate cyclase activating polypeptide on lower urinary tract functions in rats with intact or transected spinal cords.

Effects of intrathecally administered pituitary adenylate cyclase activating polypeptide-38 (PACAP-38, 0.1-30 microg) on lower urinary tract function were examined in unanesthetized, decerebrate rats with an intact spinal cord and after chronic spinal cord transection (SCT). PACAP-38 was also studied in rats with intact or bilaterally transected hypogastric nerves (HGNs), to determine if sympathetic pathways to the bladder influenced responses. In SCT rats with intact HGNs under isovolumetric conditions, 30 mug of PACAP-38 but not lower doses (0.1-10 microg) increased (mean 194%) bladder contraction amplitude (BCA). In SCT rats with sectioned HGNs, 10 microg and 30 microg of PACAP-38 increased BCA by 62% and 195%, respectively. On the other hand, during continuous infusion cystometrograms (CMGs) in SCT rats with intact or sectioned HGNs, PACAP-38 (10 microg and 30 microg) markedly reduced or completely suppressed BCA (60% and 90%, respectively) and reduced external urethral sphincter (EUS) EMG activity (58% and 91%, respectively). During CMGs in spinal cord intact rats, with intact HGNs PACAP-38 30 microg increased BCA (26%) but after HGN section PACAP-38 10 microg and 30 microg increased BCA by 21% and 35%. These results suggest that after SCT, PACAP-38 activates spinal circuitry to facilitate the parasympathetic outflow to the urinary bladder and that the elimination of sympathetic pathways enhances this effect. The decrease in BCA by PACAP-38 during CMGs in SCT rats is most reasonably attributed to a reduction in urethral outlet resistance due to suppression of excitatory EUS reflexes.