Linz W, Wiemer G, Schaper J, Zimmermann R, Nagasawa K, Gohlke P, Unger T, Schölkens B A
PGU Cardiovascular Agents, Hoechst AG, Frankfurt/Main, Germany.
Mol Cell Biochem. 1995;147(1-2):89-97. doi: 10.1007/BF00944788.
From pharmacological investigations and clinical studies, it is known that angiotensin converting enzyme (ACE) inhibitors exhibit additional local actions, which are not related to hemodynamic changes and which cannot be explained only by interference with the renin angiotensin system (RAS) by means of an inhibition of angiotensin II (ANG II) formation. Since ACE is identical to kininase II, which inactivates the nonapeptide bradykinin (BK) and related kinins, potentiation of kinins might be responsible for these additional effects of ACE inhibitors. a) In rats made hypertensive by aortic banding, the effect of ramipril in left ventricular hypertrophy (LVH) was investigated. Ramipril in the antihypertensive dose of 1 mg/kg/day for 6 weeks prevented the increase in blood pressure and the development of LVH. The low dose of ramipril (10 micrograms/kg/day for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity but also prevented LVH after aortic banding. The antihypertrophic effect of the higher and lower doses of ramipril, as well as the antihypertensive action of the higher dose of ramipril, was abolished by coadministration of the kinin receptor antagonist icatibant. In the regression study the antihypertrophic actions of ramipril were not blocked by the kinin receptor antagonist. Chronic administration of BK had similar beneficial effects in a prevention study which were abolished by icatibant and NG-nitro-L-arginine (L-NNA). In a one year study the high and low dose of ramipril prevented LVH and fibrosis. Ramipril had an early direct effect in hypertensive rats on the mRNA expression for myocardial collagen I and III, unrelated to its blood pressure lowering effect.(ABSTRACT TRUNCATED AT 250 WORDS)
从药理学研究和临床研究可知，血管紧张素转换酶（ACE）抑制剂具有额外的局部作用，这些作用与血流动力学变化无关，且不能仅通过抑制血管紧张素II（ANG II）的形成来干扰肾素血管紧张素系统（RAS）来解释。由于ACE与激肽酶II相同，激肽酶II可使九肽缓激肽（BK）及相关激肽失活，因此激肽的增强可能是ACE抑制剂这些额外作用的原因。a）在通过主动脉缩窄造成高血压的大鼠中，研究了雷米普利对左心室肥厚（LVH）的影响。雷米普利以1mg/kg/天的抗高血压剂量给药6周，可预防血压升高和LVH的发展。低剂量的雷米普利（10μg/kg/天，给药6周）对血压升高或血浆ACE活性无影响，但也可预防主动脉缩窄后的LVH。同时给予激肽受体拮抗剂艾替班特可消除高剂量和低剂量雷米普利的抗肥厚作用以及高剂量雷米普利的抗高血压作用。在回归研究中，雷米普利的抗肥厚作用未被激肽受体拮抗剂阻断。在一项预防研究中，慢性给予BK具有类似的有益作用，但被艾替班特和NG-硝基-L-精氨酸（L-NNA）消除。在一项为期一年的研究中，高剂量和低剂量的雷米普利可预防LVH和纤维化。雷米普利对高血压大鼠心肌I型和III型胶原的mRNA表达有早期直接作用，与其降压作用无关。（摘要截断于250字）
