VASCULAR CONTRACTILE POTENCY OF ENDOTHELIN-1 IS INCREASED IN THE PRESENCE OF MONOCYTES OR MACROPHAGES

Accumulation of inflammatory cells and altered responsiveness to vasoa ctive mediators are commonly observed events in atherosclerotic vessel s. We studied the effect of monocytic cells on endothelin-1 (ET-1)-ind uced contraction of strips of guinea pig carotid artery. The vascular contractile potency of ET-1 was increased markedly in the presence of human peripheral blood monocytes, guinea pig alveolar macrophages (M p hi), and the human monocytic cell line, THP-1. Specific binding of I-1 25-labeled ET-1 to these cells was detected, and Scatchard analysis in dicated a dissociation constant value of similar to 1 nM. In contrast, the human monocytic cell line, U-937, failed to bind I-125-ET-1 and d id not alter ET-1 potency, suggesting that the ability of monocytic ce lls to increase ET-1 potency requires expression of ET receptors. Sele ctive inhibition of ET-1 binding to vascular smooth muscle with BQ-123 , an ET(A) receptor antagonist that does not inhibit ET-1 binding to m onocytes, resulted in complete inhibition of vascular contraction. The se data indicate that ET-1-induced vasoconstriction may be increased b y monocytic cells via stimulation of monocyte endothelin receptors.