Yau L, Pinsk M, Zahradka P
Division of Cardiovascular Sciences, Department of Physiology, University of Manitoba, Winnipeg, Canada.
Arch Biochem Biophys. 1996 Apr 1;328(1):115-21. doi: 10.1006/abbi.1996.0150.
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 B1 and B2 receptors 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 B1 and B2 receptor 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, PGE2 and PGI2 (prostacyclin), on A10 cells. PGE2 caused a decrease in RNA synthesis, thus mimicking the effect of BK, while PGI2 did not. Therefore, the inhibition of RNA synthesis in A10 vascular smooth muscle cells by BK requires both B1 and B2 receptor subtypes and this action of BK is apparently mediated by de novo synthesis of prostaglandins.
血管紧张素转换酶抑制剂治疗心脏病的疗效部分归因于缓激肽（BK）的蓄积。由于BK可通过影响细胞增殖发挥作用，我们选择研究BK对A10血管平滑肌细胞生长的影响。通过配体结合研究来确定A10细胞上存在哪些BK受体亚型，结果显示B1和B2受体的数量大致相等。对RNA合成的检测表明，BK以剂量依赖的方式抑制尿苷掺入。RNA合成的这种减少被B1和B2受体拮抗剂以及添加环氧化酶抑制剂吲哚美辛所阻断。后一结果表明前列腺素介导BK的生物学作用。因此，我们检测了两种前列腺素PGE2和PGI2（前列环素）对A10细胞的直接影响。PGE2导致RNA合成减少，从而模拟了BK的作用，而PGI2则没有。因此，BK对A10血管平滑肌细胞RNA合成的抑制需要B1和B2受体亚型，且BK的这一作用显然是由前列腺素的从头合成介导的。
