[Vasoconstricting effect of endothelin. Interaction with atrial natriuretic factor, sodium nitroprusside, cicletanine...

The contractile properties of endothelin (ENDO) and its interactions with some putative antagonists were investigated in endothelium free ring of rat aorta. ENDO induced a slowly developing contraction which is only partially affected by sodium nitroprusside (10(-8) M - 10(-5) M) and to a lesser extend by the calcium antagonist nifedipine (10(-8) M - 10(-5) M). Atrial natriuretic factor (ANF) (10(-9) M - 10(-8) M), cicletanine (3.10(-5) M - 3.10(-4) M) and quercetin (10(-5) M - 10(-4) M) induced a dose dependent relaxation in ENDO precontracted preparations. ANF was less effective in inhibiting ENDO- than phenylephrine precontracted aorta. In addition, the ANF vasodilating effect upon ENDO contraction is potentiated by cicletanine (10(-4) M). The protein kinase C inhibitor phloretin, induced a dose-dependent relaxation (10(-5) M - 3.10(-4) M) in both ENDO and phorbol 12, 13-dibutyrate precontracted aorta. Whereas H7 (10(-5) M - 3.10(-4) M) an other protein kinase C inhibitor was only effective in ENDO-induced contraction. These data indicate that in isolated rat aorta, the contraction induced by ENDO does not mainly occur through membrane potential-dependent calcium channels. The vasoconstrictor mechanism of ENDO, which is different from the one triggered by phenylephrine could involve activation of protein kinase C.