Role of the nitric oxide-cyclic GMP pathway in regulation of vaginal blood flow.
The regulatory role of nitric oxide (NO) in vaginal perfusion remains unclear. We used specific inhibitors of enzymes in the NO-cyclic GMP (NO-cGMP) pathway and investigated their effects on vaginal blood flow in the rabbit. NO synthase (NOS) activity was similar in both the proximal and distal rabbit vagina; whereas, arginase activity was 3.4-fold higher in the distal vagina. Intravenous administration of the NOS inhibitor L-NAME resulted in a 66% reduction in genital tissue oxyhemoglobin and a 53% reduction in vaginal blood flow. This attenuation occurred despite a 20-30% increase in systemic arterial pressure. The arginase inhibitor ABH caused a 2.1-fold increase in genital tissue oxyhemoglobin and 34% increase in vaginal blood flow. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one and the phosphodiesterase type 5 inhibitor sildenafil caused in a 37% reduction and a 44% increase in vaginal blood flow, respectively. These observations suggest that the NO-cGMP pathway is an important regulator of vaginal hemodynamics.
Kim
S W
SW
Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
Jeong
S-J
SJ
Munarriz
R
R
Kim
N N
NN
Goldstein
I
I
Traish
A M
AM
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017078:Laser-Doppler Flowmetry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012726:Sexual Behavior, Animal / Q000502:physiology*; D000068677:Sildenafil Citrate; D013450:Sulfones; D014621:Vagina / Q000098:blood supply* / Q000294:innervation
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011810:Quinoxalines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester