Endothelin-1-induced pulmonary vasoreactivity is regulated by ET(A) and ET(B) receptor interactions

Roles of endothelin (ET) receptors (R) and of the endothelium on ET-1-induced pulmonary vasoreactivity are subjects of debate. This stems from endothelial ET(B)-R that can release both vasodilators and vasoconstrictors. The aim of this study was to evaluate the roles of the endothelium and of ET-Rs on ET-1-induced pulmonary vasoreactivity.

Pharmacological experiments were performed in isolated rat lungs and in pulmonary resistance arteries.

In isolated lungs, ET-1 and the selective ET(B)-R agonist sarafotoxin 6c (S6c) induced a similar vasoconstriction. ET-1 constriction was reduced by a selective ET(A)-R antagonist; however, the selective ET(B)-R antagonist had no significant effect. In preconstricted lungs, ET(B)-R stimulation caused mild vasodilation at low concentrations but severe vasoconstriction at higher concentrations. In isolated arteries, responses to ET-1 and S6c were not different and unaffected by removal of endothelium. Interestingly, concentrations of ET(A)-R and ET(B)-R antagonists that only mildly reduced ET-1 vasoconstriction when used alone, prevented maximal constriction and greatly reduced vascular sensitivity to ET-1 when used in combination.

In rat lungs, both ET(A)-R and ET(B)-R contribute to ET-1-induced pulmonary vasoconstriction with evidence of interaction between receptors. A mild vasodilator role of the endothelial ET(B)-R is evident only at low agonist concentration and when baseline vascular tone is increased.