Pharmacological Properties of Endothelin-1 in the Rabbit Corpus Cavernosum

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 α₁-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 ET_A (BQ123) and ET_B (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^-4M) and ET-1 (10^-10-10^-6M) produced a concentration-dependent contraction in rabbit CSM strips. The EC₅₀ values were 1.7×10^-7 M ±1.1 and 3.4×10^-9 M ± 1.5, respectively. BQ123 10^-5M significantly inhibited ET-1-mediated CSM contractions more than BQ788 10^-5M (both ANOVA p<0.01). The EC₅₀ were 1.3×10^-6M ±2.6 and 2.0×10^-7M ± 2.1, respectively. Neither the ET_A or ET_B receptor antagonist had a significant influence on α₁-adrenergic receptor-mediated CSM contraction. Conclusion: ET_A receptors may play a greater role than ET_B receptors in ET-1-induced rabbit CSM contraction and the detumescence process. The α₁-adrenergic-dependent pathway does not involve the ET_A or ET_B receptors.