Oda S, Sano T, Morishita Y, Matsuda Y
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
J Pharmacol Exp Ther. 1992 Oct;263(1):241-5.
Atrial natriuretic peptide (ANP) is known to inhibit the aldosterone production by adrenal glomerulosa cells stimulated by angiotensin II. However, the mechanism of the inhibitory action is still somewhat uncertain. In this study we used HS-142-1, a novel nonpeptide antagonist for ANP receptor, to examine the role of cyclic GMP in the inhibition of aldosterone production by ANP. Aldosterone production by isolated bovine adrenal glomerulosa cells was stimulated by angiotensin II at a concentration of 10(-8) M. The angiotensin II-stimulated aldosterone production was inhibited by rat ANP in a dose-dependent manner at concentrations ranging from 10(-9) to 10(-7) M. HS-142-1, at concentrations of 0.1 to 100 micrograms/ml, reversed the inhibition by ANP of the angiotensin II-stimulated aldosterone production. On the other hand, intracellular concentration of cyclic GMP increased rapidly as early as 1 min after the exposure of the cells to 10(-8) M ANP in the presence of angiotensin II. This increase of intracellular cyclic GMP level was again reduced by HS-142-1 at concentrations similar to those that reversed the inhibition by ANP of the aldosterone production. These results suggest that ANP inhibits the aldosterone production through a guanylyl cyclase-coupled pathway in adrenal glomerulosa cells.
已知心房利钠肽（ANP）可抑制血管紧张素II刺激的肾上腺球状带细胞产生醛固酮。然而，其抑制作用的机制仍存在一定不确定性。在本研究中，我们使用了一种新型的ANP受体非肽拮抗剂HS - 142 - 1，来研究环磷酸鸟苷（cGMP）在ANP抑制醛固酮产生过程中的作用。用浓度为10(-8) M的血管紧张素II刺激分离的牛肾上腺球状带细胞产生醛固酮。大鼠ANP在浓度范围为10(-9)至10(-7) M时，以剂量依赖的方式抑制血管紧张素II刺激的醛固酮产生。浓度为0.1至100微克/毫升的HS - 142 - 1可逆转ANP对血管紧张素II刺激的醛固酮产生的抑制作用。另一方面，在血管紧张素II存在的情况下，细胞暴露于10(-8) M ANP后，最早在1分钟时细胞内环磷酸鸟苷的浓度就迅速升高。与逆转ANP对醛固酮产生抑制作用的浓度相似的HS - 142 - 1，再次降低了细胞内环磷酸鸟苷水平的这种升高。这些结果表明，ANP通过肾上腺球状带细胞中的鸟苷酸环化酶偶联途径抑制醛固酮的产生。
