Goldberg M R, de Mey C, Wroblewski J M, Li Q, Schroeter V, Belz G G
Merck Research Laboratories, West Point, PA 19486, USA.
Clin Pharmacol Ther. 1996 Jan;59(1):72-82. doi: 10.1016/S0009-9236(96)90026-0.
This double-blind, placebo-controlled crossover study was designed to differentiate the pharmacodynamic effects of the angiotensin II receptor antagonist losartan from the angiotensin converting enzyme inhibitor enalapril. Effects of placebo, enalapril (10 mg), and losartan (20 and 100 mg) on local venous and systemic pressor responses to angiotensin I and II were compared in eight healthy male subjects. Treatments were administered orally approximately 4 hours before agonist infusions into a dorsal hand vein. Local changes in hand vein diameter and systemic blood pressure were monitored during the infusions. The 100 mg dose of losartan attenuated local venoconstrictor and systemic pressor responses to angiotensin I and II. In contrast, enalapril blocked only responses to angiotensin I. Both losartan and enalapril increased plasma renin concentration compared with placebo. These results are consistent with direct antagonism of angiotensin II receptors by losartan and with indirect effects of enalapril through inhibition of angiotensin converting enzyme.
这项双盲、安慰剂对照的交叉研究旨在区分血管紧张素II受体拮抗剂氯沙坦与血管紧张素转换酶抑制剂依那普利的药效学作用。在8名健康男性受试者中,比较了安慰剂、依那普利(10毫克)以及氯沙坦(20毫克和100毫克)对局部静脉和全身对血管紧张素I和II的升压反应的影响。在向手背静脉输注激动剂前约4小时口服给药。输注期间监测手部静脉直径和全身血压的局部变化。100毫克剂量的氯沙坦减弱了局部静脉收缩和全身对血管紧张素I和II的升压反应。相比之下,依那普利仅阻断对血管紧张素I的反应。与安慰剂相比,氯沙坦和依那普利均增加了血浆肾素浓度。这些结果与氯沙坦对血管紧张素II受体的直接拮抗作用以及依那普利通过抑制血管紧张素转换酶的间接作用一致。