INHIBITION OF RNA-SYNTHESIS BY BRADYKININ INVOLVES BOTH THE B-1 AND B-2 RECEPTOR SUBTYPES

The efficacy of angiotensin converting enzyme inhibitors in the treatm ent of heart disease is due in part to the accumulation of bradykinin (BK). Since BK can exert its effect by influencing cell proliferation, we chose to study the effect of BK on the growth of A10 vascular smoo th muscle cells. Ligand binding studies to determine which BK receptor subtypes are present on A10 cells showed that both B-1 and B-2 recept ors were present in approximately equal numbers. Examination of RNA sy nthesis demonstrated that BK inhibits uridine incorporation in a dose- dependent manner. This decrease in RNA synthesis was blocked by both B 1 and Bz receptor antagonists, as well as by addition of indomethacin, a cyclooxygenase inhibitor. The latter result suggested that prostagl andins mediate the biological actions of BK. Consequently, we examined the direct effect of two prostaglandins, PGE(2) and PGI(2) (prostacyc lin), on A10 cells. PGE(2) caused a decrease in RNA synthesis, thus mi micking the effect of BK, while PGI(2) did not. Therefore, the inhibit ion of RNA synthesis in A10 vascular smooth muscle cells by BK require s both B-1 and B-2 receptor subtypes and this action of BR is apparent ly mediated by de novo synthesis of prostaglandins. (C) 1996 Academic Press, Inc.