HUMAN ENDOTHELIN ET(A) RECEPTOR ANTISENSE OLIGODEOXYNUCLEOTIDES INHIBIT ENDOTHELIN-1 EVOKED VASOCONSTRICTION

Antisense oligodeoxynucleotides to endothelin ET(A) receptor mRNA were used to characterize vascular smooth muscle receptors. The concentrat ion-response curve showed a significant attenuation of endothelin-1-in duced contraction in circular segments of the human superficial tempor al artery. Endothelin ET(B) receptor antisense or mismatch oligodeoxyn ucleotides showed no alteration of the endothelin-1-induced contractio n. Complementary experiments with the selective endothelin ET(A) recep tor antagonist FR139317 demonstrated a shift of the concentration-resp onse curve to the right in a competitive manner (pA(2) = 6.93). The sp ecific method of using the receptor antisense oligodeoxynucleotides ap proach revealed the presence of endothelin ET(A) receptors mediating c ontraction in the human superficial temporal artery.