Differing effects of N(G)-monomethyl L-arginine and 7-nitroindazole on detrusor activity

Previous studies reported that nitric oxide (NO) synthase (NOS) inhibition decreases micturition volume threshold (MVT), the volume required to produce a centrally mediated micturition contraction, and that NO can be released from urothelium by means of certain stimuli. With elucidation of multiple isoforms of NOS, studies were performed to determine whether inhibition of specific isoforms of NOS altered MVT in different ways.

In naive, anesthetized cats, the urinary bladder was exposed by means of a midline abdominal incision and cannulated through a slit in the internal urethra approximately 4-5 cm distal to the neck of the bladder. The left renal artery and left radial vein were cannulated for the intra-arterial and intravenous administration of drugs, respectively. All nerves were left intact. A control MVT was determined by slowly infusing saline into the bladder at a rate of 0.018 mL/kg per minute. Varying doses of L-NMMA (N(G)-monomethyl-L-arginine) or 7-NI (7-nitro indazole) were administered and the MVT was again determined.

Inhibition of endothelial NOS (eNOS), by L-NMMA, or neuronal NOS (nNOS), by 7-NI, produces varying effects on certain detrusor activities and that inhibition of different isoforms of NOS produces qualitatively different effects. L-NMMA significantly decreases MVT (up to 60% decrease), whereas 7-NI significantly increases MVT (over 300% increase). L-NMMA increases frequency and onset of small bladder contractions, whereas 7-NI produces opposite effects.

The results suggest that detrusor relaxation and contractility may be modulated by NO levels and that NO released from the urothelium may be a mediator of detrusor relaxation during the storage phase of micturition.