FUNCTIONAL COMPARISON OF ENDOTHELIN RECEPTORS IN HUMAN AND RAT PULMONARY-ARTERY SMOOTH-MUSCLE

The receptors mediating arterial smooth muscle contraction to endothel ins (ET) differ among species and origin of vascular bed. We character ized ET receptors mediating contraction of endothelium-denuded human i ntralobar pulmonary artery (hIPA) and rat intralobar (rIPA) and extral obar left branch (rLPA) pulmonary artery with ET-1, ET-2, ET-3, sarafo toxin S6c, sarafotoxin S6b, and ET receptor antagonists in vitro. Rat aorta was studied for comparison. Each vascular segment showed concent ration-dependent contraction with a rank order sensitivity (pot) profi le of ET-1 greater than or equal to ET-2 = sarafotoxin S6b > ET-3. Max imum contraction to ET-1 was greater than to sarafotoxin S6c in all pr eparations. Responses of rIPA and rLPA to sarafotoxin S6c were conspic uous when compared with hIPA or aorta. The ETA receptor blockers BQ-12 3 and EMS-182874 competitively antagonized ET-1 responses of hIPA and aorta, but not rLPA. The ETB receptor antagonist BQ-788 attenuated con tractions of rIPA and rLPA to ET-3 and sarafotoxin S6c, respectively. In conclusion, ET(B)-mediated contraction of endothelium-denuded condu it pulmonary arteries varies among species and may contribute more to contraction of rIPA and rLPA than of hIPA and aorta, although maximum ETB-mediated contraction is smaller than that mediated by the ETA rece ptor.