title: Nitric oxide signaling pathways involved in the inhibition of spontaneous activity in the guinea pig prostate.
abstract: OBJECTIVE
  We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates.
  
  
  METHODS
  Conventional intracellular microelectrode and tension recording techniques were used.
  
  
  RESULTS
  The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA p<0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 μM) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p<0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 μM) and the PDE5 inhibitor dipyridamole (1 μM) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p<0.05).
  
  
  CONCLUSIONS
  The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia.
authors.affiliation: Medicinal Chemistry and Drug Action, Department of Pharmaceutical Biology and Pharmacology, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia.
authors.forename: Anupa
authors.initials: A
authors.lastname: Dey
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lang
authors.forename: Betty
authors.initials: B
authors.lastname: Exintaris
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D008297:Male; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide