title: Endothelium dependent relaxation in rabbit genital resistance arteries is predominantly mediated by endothelial-derived hyperpolarizing factor in females and nitric oxide in males.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Glasgow, Glasgow, UK. j.morton@research.gla.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Morton
authors.forename: V M
authors.initials: VM
authors.lastname: Jackson
authors.forename: C J
authors.initials: CJ
authors.lastname: Daly
authors.forename: J C
authors.initials: JC
authors.lastname: McGrath
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D008297:Male; D009126:Muscle Relaxation; D009569:Nitric Oxide / Q000502:physiology*; D010413:Penis / Q000098:blood supply* / Q000502:physiology*; D011817:Rabbits; D012727:Sex Characteristics; D014621:Vagina / Q000098:blood supply* / Q000502:physiology*; D014655:Vascular Resistance
chemical_list: D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide