Inhibition of RNA Synthesis by Bradykinin Involves Both the B1and B2Receptor Subtypes

The efficacy of angiotensin converting enzyme inhibitors in the treatment 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 smooth muscle cells. Ligand binding studies to determine which BK receptor subtypes are present on A10 cells showed that both B1and B2receptors were present in approximately equal numbers. Examination of RNA synthesis demonstrated that BK inhibits uridine incorporation in a dose-dependent manner. This decrease in RNA synthesis was blocked by both B1and B2receptor antagonists, as well as by addition of indomethacin, a cyclooxygenase inhibitor. The latter result suggested that prostaglandins mediate the biological actions of BK. Consequently, we examined the direct effect of two prostaglandins, PGE2and PGI2(prostacyclin), on A10 cells. PGE2caused a decrease in RNA synthesis, thus mimicking the effect of BK, while PGI2did not. Therefore, the inhibition of RNA synthesis in A10 vascular smooth muscle cells by BK requires both B1and B2receptor subtypes and this action of BK is apparently mediated byde novosynthesis of prostaglandins.