Pharmacological properties of endothelin-1 in the rabbit corpus cavernosum

In Vivo. 2006 Mar-Apr;20(2):243-6.

Abstract

Background: Endothelin (ET-1) may play a role in the regulation of erection but this has not been conclusively demonstrated. Augmented cavernosal smooth muscle (CSM) contraction in the rat occurs following exposure to both ET-1 and phenylephrine (PE; alpha-1 agonist). The aim of this study was to assess the effect of ET-1 and its possible role in the alpha1-adrenergic pathway during the erectile process.

Materials and methods: Organ bath studies were performed on CSM strips of penises obtained from 12 age-matched New Zealand White rabbits. The effect of ET-1 and PE alone on CSM tone in the absence and presence of ETA (BQ123) and ETB (BQ788) antagonists was assessed. Tissue responses were measured as tension (newton, N). EC50 values are expressed as mean +/- S.E.M.

Results: PE (10(8) - 10(-4) M) and ET-1 (10(-10) - 10(-6) M) produced a concentration-dependent contraction in rabbit CSM strips. The EC50 values were 1.7 x 10(-7) M +/- 1.1 and 3.4 x 10(-9) M +/- 1.5, respectively. BQ123 10(-5) M significantly inhibited ET-1-mediated CSM contractions more than BQ788 10(-5) M (both ANOVA p<0.01). The EC50 were 1.3 x 10(-6) M +/- 2.6 and 2.0 x 10(-7) M +/- 2.1, respectively. Neither the ETA or ETB receptor antagonist had a significant influence on alpha1-adrenergic receptor-mediated CSM contraction.

Conclusion: ETA receptors may play a greater role than ETB receptors in ET-1-induced rabbit CSM contraction and the detumescence process. The a1-adrenergic-dependent pathway does not involve the ETA or ETB receptors.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Endothelin Receptor Antagonists
  • Endothelin-1 / antagonists & inhibitors
  • Endothelin-1 / pharmacology*
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiopathology
  • Oligopeptides / pharmacology
  • Penile Erection / drug effects*
  • Penis / drug effects*
  • Penis / metabolism
  • Peptides, Cyclic / pharmacology
  • Phenylephrine / pharmacology
  • Piperidines / pharmacology
  • Rabbits

Substances

  • Adrenergic alpha-Agonists
  • Antihypertensive Agents
  • Drug Combinations
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Phenylephrine
  • BQ 788
  • cyclo(Trp-Asp-Pro-Val-Leu)