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

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_A and ET_B receptors in haemorrhoid tissue.

Protein expression of ET-1, ET_A and ET_B 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.

Dense binding of [¹²⁵ I]-ET-1 to haemorrhoidal sections was reduced by selective receptor antagonists. A higher density of ET_B than ET_A receptors was found in haemorrhoidal, than in control rectal tissue and confirmed by Western blot analysis. ET_A and ET_B receptors were localized to smooth muscle of haemorrhoidal arteries and veins, with ET_B receptors on the endothelium. Human colonic and rectal arteries and veins were similarly sensitive to ET-1 and affected by the ET_A selective antagonist, but sarafotoxin S6a-induced contractions were more pronounced in veins and antagonized by a selective ET_B receptor antagonist.

ET_A and ET_B receptors are present in human haemorrhoids with ET_B receptors predominating. ET_A 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_B receptors at low concentrations. Selective ET_B agonists may have therapeutic potential to reduce congestion of the haemorrhoidal venous sinusoids.