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International Journal of Impotence Research (2003) 15, 355361
& 2003 Nature Publishing Group All rights reserved 0955-9930/03 $25.00www.nature.com/ijirRole of the nitric oxide-cyclic GMP pathway in regulation of
vaginal blood flowSW Kim1, S-J Jeong2, R Munarriz2, NN Kim2, I Goldstein2 and AM Traish2,3*1Department of Urology, Seoul National University College of Medicine, Seoul, Korea; 2Department of Urology, Boston
University School of Medicine, Boston, Massachusetts, USA; and3Department of Biochemistry, Boston University School
of Medicine, Boston, Massachusetts, USAThe 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
2030% 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.International Journal of Impotence Research (2003) 15, 355361. doi:10.1038/sj.ijir.3901038Keywords: nitric oxide; L-NAME; guanylate cyclase; arginase; female genital arousal; oximetry;
laser Doppler flowmetryIntroductionThe arousal phase of the female sexual response
involves, in part, local regulatory mechanisms that
modulate tone in the clitoral and labial erectile
tissue and the vascular and nonvascular smooth
muscle of the vagina.1,2 Immunohistochemical studies in human vaginal tissues have identified nerve
fibers containing neuropeptide Y, vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS),
calcitonin gene-related peptide and substance P.3
Previous studies have suggested that VIP may be
involved in the regulation of clitoral and vaginal
smooth muscle tone, but no conclusive experimental evidence of its functional involvement has been
forthcoming.38Cellek and Moncada9 demonstrated that electrical
field stimulation causes nonadrenergic, noncholinergic (NANC) relaxation responses that are
mediated by nitric oxide (NO) in rabbit clitoral
corpus cavernosum. While the NO-cyclic GMP (NO-
cGMP) pathway has been reported to...