Endothelium dependent relaxation in rabbit genital resistance arteries is predominantly mediated by endothelial-derived hyperpolarizing factor in females and nitric oxide in males

• Published in: The Journal of urology Vol. 177; no. 2; p. 786
• Main Authors: Morton, J S, Jackson, V M, Daly, C J, McGrath, J C
• Format: Journal Article
• Language: English
• Published: United States 01.02.2007
• Subjects: Animals; Biological Factors - physiology; Endothelium, Vascular - physiology; Female; Male; Muscle Relaxation; Nitric Oxide - physiology; Penis - blood supply; Penis - physiology; Rabbits; Sex Characteristics; Vagina - blood supply; Vagina - physiology; Vascular Resistance
• ISSN: 0022-5347
• DOI: 10.1016/j.juro.2006.09.072

In nongenital arteries a sex difference has been postulated in the dominant endothelium-derived relaxant factor(s), eg nitric oxide, prostacyclin or endothelial-derived hyperpolarizing factor. Knowledge of endothelium-derived relaxant factor mechanisms in genital tissues could influence the development of novel treatments for sexual dysfunction. We compared nitric oxide and endothelial-derived hyperpolarizing factor contributions to acetylcholine induced relaxation in the genital arteries of the 2 sexes. Male dorsal and cavernous penile arteries, and female extravaginal and intravaginal arteries from New Zealand White rabbits were studied. Acetylcholine concentration-vasodilator response curves were constructed in the presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester, K(+) channel blockers (apamin and charybdotoxin) or a combination. Indomethacin was present throughout to exclude prostacyclins. Extravaginal artery relaxation was predominantly endothelial-derived hyperpolarizing factor induced. Apamin plus charybdotoxin decreased maximal relaxations from a mean +/- SEM of 77% +/- 4% to 23% +/- 3% in 6 preparations (p <0.01). However, nitric oxide and endothelial-derived hyperpolarizing factor contributed to overall function. Dorsal artery relaxation was largely nitric oxide induced. Nomega-nitro-L-arginine methyl ester decreased maximal relaxations from 90% +/- 3% to 41% +/- 9% (p <0.001) with no endothelial-derived hyperpolarizing factor involvement (p >0.05). In cavernous and intravaginal arteries nitric oxide and endothelial-derived hyperpolarizing factor contributed to acetylcholine induced relaxation, while nitric oxide predominated. Blocking nitric oxide synthase or K(+) channels indicated that myogenic tone and constitutive activity of endothelium-derived relaxant factors were present. Vasodilator nerve mediated responses were influenced by each with the former more effective. Vaginal inflow arteries showed a dominance of endothelial-derived hyperpolarizing factor, contrasting with nitric oxide in penile arteries. Penile arteries followed the trend that endothelial-derived hyperpolarizing factor involvement increased with decreasing vessel caliber, while the reverse was demonstrated in female arteries.