Vasoconstricting effect of endothelin. Interaction with atrial natriuretic factor, sodium nitroprusside, cicletanine and nifedipine
Auguet, M.; Delaflotte, S.; Chabrier, P.E.; Braquet, P.
Archives des Maladies du Coeur et des Vaisseaux 82(7): 1169-1172
1989
ISSN/ISBN: 0003-9683 PMID: 2530950 Document Number: 334223
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.