Angiotensin-converting enzyme inhibition improves cardiac function. Role of bradykinin.
Angiotensin-converting enzyme inhibition improves cardiac function. Role of bradykinin.
复制标题
血管紧张素转换酶抑制可改善心脏功能。
作者：
P. Gohlke;Wolfgang Linz;B. Scholkens;I. Kuwer;S. Bartenbach;A. Schnell;Thomas Unger
研究了血管紧张素转换酶（ACE）抑制剂雷米普利（0.01和1 mg/kg/天）长期低剂量和高剂量给药对高血压和左心室肥大发展以及心脏功能和生化改变的影响。内源性缓激肽增强对ACE抑制剂作用的贡献通过用缓激肽B2受体拮抗剂Hoe 140（500 μ g/kg/天SC）从6至20周龄共处理大鼠来评估。高剂量而非低剂量ACE抑制剂治疗可预防高血压和左心室肥大的发生。慢性缓激肽受体阻滞剂不能减弱雷米普利的抗高血压和抗肥大作用。大剂量雷米普利治疗可改善心功能，表现为左心室压力（29.9%）、dP/dtmax（34.9%）和冠状动脉流量（22.1%）增加，而心率无变化。冠脉流出液中乳酸脱氢酶、肌酸激酶活性和乳酸浓度分别降低39.3%、55.5%和66.7%。心肌组织中糖原和富含能量的磷酸盐ATP和磷酸肌酸的浓度分别增加了31.3%、39.9%和73.7%，而乳酸则减少了20.8%。长期低剂量ACE抑制剂治疗导致心脏动力学和心脏代谢的变化模式与高剂量相似。慢性缓激肽受体阻滞剂可消除ACE对心功能和代谢的所有影响。（250字处删节）
The effect of chronic low- and high-dose treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on the development of hypertension and left ventricular hypertrophy as well as on functional and biochemical alterations of the heart was studied in stroke-prone spontaneously hypertensive rats treated prenatally and subsequently up to the age of 20 weeks. The contribution of endogenous bradykinin potentiation to the ACE inhibitor actions was assessed by cotreatment of rats with the bradykinin B2-receptor antagonist Hoe 140 (500 micrograms/kg per day SC) from 6 to 20 weeks of age. High- but not low-dose ACE inhibitor treatment prevented the development of hypertension and left ventricular hypertrophy. Chronic bradykinin receptor blockade did not attenuate the antihypertensive and antihypertrophic actions of ramipril. High-dose ramipril treatment improved cardiac function, as demonstrated by an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and coronary flow (22.1%), without a change in heart rate. The activities of lactate dehydrogenase and creatine kinase and lactate concentration in the coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatment led to a pattern of changes in cardiodynamics and cardiac metabolism similar to that observed with the high dose. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by chronic bradykinin receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)