ENDOTHELIN RECEPTOR SUBTYPES IN RESISTANCE ARTERIES FROM HUMANS AND RATS

Objective: Endothelins bind to different receptor subtypes identified as ET(A) and ET(B) receptors. ET(A) receptors are present on smooth muscle cells of blood vessels. ET(B) receptors seem to predominate on endothelial cells of blood vessels, but may also be present on smooth muscle in some vascular beds. The aim of this study was to investigate the distribution of ET(A) and ET(B) receptors in human and in rat resistance arteries. Methods: Contractile responses to endothelin-1 and to the ET(B) agonist sarafotoxin S6c were investigated in human subcutaneous resistance arteries and in rat mesenteric resistance arteries mounted on a wire myograph. Results: Contractile responses to endothelin-1 were significantly reduced by the ET(A) selective antagonists BQ123 or BQ610 in human resistance arteries, and were almost abolished by the antagonists in rat arteries. The ET(B) agonist sarafotoxin S6c induced smaller responses than endothelin-1. When responses to sarafotoxin S6c were obtained in the presence of BQ610, the relatively small contractile response remained. It was slightly enhanced if the responses were obtained in the presence of the nitric oxide synthase inhibitor L-NAME or after removal of the endothelium. Conclusions: Vasoconstrictor ET(B) receptors appear to be present in resistance vessels isolated from subcutaneous fat in humans and from the mesentery in rats, but their contribution to endothelin mediated constriction is small, particularly in rat resistance arteries. ET(A) receptors appear to be the more important endothelin receptor subtype in the human and rat resistance arteries examined.