s6c-sarafotoxin and Hirschsprung-Disease

Hirschsprung's disease is associated with defects in the endothelin-3 and endothelin B receptor genes.. To assess the in vivo vasomotor responses to endothelin B receptor stimulation in patients with Hirschsprung's disease.. Forearm blood flow was measured using venous occlusion plethysmography in 10 patients with Hirschsprung's disease and 10 matched healthy controls during intra-brachial infusion of the highly selective endothelin B receptor agonist, sarafotoxin S6c. To simulate endothelin B receptor dysfunction, sarafotoxin S6c was co-infused with the highly selective endothelin B receptor antagonist, BQ-788, in six of the healthy controls.. Sarafotoxin S6c caused a brief initial vasodilatation followed by a slow-onset, sustained vasoconstriction (p<0.001). Compared to control subjects, patients with Hirschsprung's disease had a substantial impairment of the initial vasodilatation whilst producing a more pronounced subsequent vasoconstriction (p<0.001). In healthy controls, co-infusion of BQ-788 and sarafotoxin S6c caused a similar pattern of responses to those obtained in patients with Hirschsprung's disease: abolition of the initial vasodilatation and augmentation of subsequent vasoconstriction (p<0.001).. In the majority of patients with Hirschsprung's disease, there is a functional defect of the vascular endothelin B receptor.

Topics: Adult; Endothelin Receptor Antagonists; Female; Forearm; Hirschsprung Disease; Humans; Male; Oligopeptides; Piperidines; Receptor, Endothelin B; Receptors, Endothelin; Regional Blood Flow; Vasoconstrictor Agents; Vasomotor System; Viper Venoms