Endothelin-1 and its receptors on haemorrhoidal tissue: a potential site for therapeutic intervention.

Background And Purpose: Haemorrhoids is a common anorectal condition affecting millions worldwide. We have studied the effect of endothelin-1 (ET-1) and the role of endothelin ET and ET receptors in haemorrhoid tissue.

Experimental Approach: Protein expression of ET-1, ET and ET receptors were compared between haemorrhoids and normal rectal submucosa using Western blot analysis, with the localization of proteins determined by autoradiography and immunohistochemistry. Effects of ET-1 and sarafotoxin 6a on human colonic and rectal arteries and veins was assessed by wire myography and the involvement of receptor subtypes established by selective antagonists.

Key Results: Dense binding of [ I]-ET-1 to haemorrhoidal sections was reduced by selective receptor antagonists. A higher density of ET than ET receptors was found in haemorrhoidal, than in control rectal tissue and confirmed by Western blot analysis. ET and ET receptors were localized to smooth muscle of haemorrhoidal arteries and veins, with ET receptors on the endothelium. Human colonic and rectal arteries and veins were similarly sensitive to ET-1 and affected by the ET selective antagonist, but sarafotoxin S6a-induced contractions were more pronounced in veins and antagonized by a selective ET receptor antagonist.

Conclusions And Implications: ET and ET receptors are present in human haemorrhoids with ET receptors predominating. ET receptors are activated by ET-1 to mediate a contraction in arteries and veins, but the latter are selectively activated by sarafotoxin S6a - a response that involves ET receptors at low concentrations. Selective ET agonists may have therapeutic potential to reduce congestion of the haemorrhoidal venous sinusoids.