Yasujima M, Abe K, Tanno M, Omata K, Yoshinaga K
Jpn Circ J. 1984 Feb;48(2):173-9. doi: 10.1253/jcj.48.173.
Three structurally different drugs, MK421, SA446 and captopril, are angiotensin converting enzyme inhibitors. They induced a significantly greater fall in systolic blood pressure in sodium depleted rats than in sodium repleted ones. The combined administration of vasopressin or norepinephrine with MK421 eliminated the hypertensive effect of vasopressin or norepinephrine. Urinary kallikrein and kinin excretion were increased by MK421, SA446 or captopril in the sodium depleted rats whereas any significant changes in them were not observed in the sodium repleted rats. The combined administration of norepinephrine with MK421 induced further increases in urinary kallikrein and kinin excretion when compared to rats infused with norepinephrine alone, whereas the combined administration of vasopressin with MK421 did not induce any changes in them when compared to rats infused with vasopressin alone. Chronic infusion of captopril for up to 6 days in the rats induced a reduction of the vascular response to exogenous bradykinin; the blood pressure fall was less than that of the controls by 17% on Day 2 and by 18% on Day 6. These results indicate that the hypotensive response to angiotensin converting enzyme inhibitors was in part associated with the enhanced renal and vascular smooth muscle kallikrein-kinin system.
三种结构不同的药物，MK421、SA446和卡托普利，均为血管紧张素转换酶抑制剂。与钠充足的大鼠相比，它们使钠缺乏的大鼠收缩压下降幅度明显更大。血管加压素或去甲肾上腺素与MK421联合给药可消除血管加压素或去甲肾上腺素的升压作用。MK421、SA446或卡托普利可使钠缺乏大鼠的尿激肽释放酶和激肽排泄增加，而在钠充足的大鼠中未观察到它们有任何显著变化。与单独输注去甲肾上腺素的大鼠相比，去甲肾上腺素与MK421联合给药可使尿激肽释放酶和激肽排泄进一步增加，而与单独输注血管加压素的大鼠相比，血管加压素与MK421联合给药对它们未产生任何影响。在大鼠中持续输注卡托普利长达6天可导致对外源性缓激肽的血管反应降低；血压下降幅度在第2天比对照组少17%，在第6天比对照组少18%。这些结果表明，对血管紧张素转换酶抑制剂的降压反应部分与肾和血管平滑肌激肽释放酶-激肽系统的增强有关。
