Maxwell A J, Husseini W K, Piedimonte G, Hoffman J I
Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Am J Physiol. 1995 Sep;269(3 Pt 2):H1016-29. doi: 10.1152/ajpheart.1995.269.3.H1016.
To determine whether neutral endopeptidase (NEP) and kininase II (angiotensin-converting enzyme, ACE) influence coronary hemodynamics, we compared the effects of inhibiting NEP, ACE, or both before and after isoproterenol (50 mg/kg ip). We measured flow and resistance using radioactive microspheres in 90 anesthetized rats which received the NEP inhibitor phosphoramidon (2.5 mg/kg), the ACE inhibitor captopril (2.5 mg/kg), both combined, or vehicle alone. Before isoproterenol, inhibiting NEP, ACE, or both increased left ventricular blood flow by 48 +/- 10 (SE), 33 +/- 9, and 10 +/- 6%, respectively, and decreased left ventricular vascular resistance by 26 +/- 6, 31 +/- 10, and 10 +/- 6%, respectively. After isoproterenol, NEP inhibition augmented the decrease in left ventricular vascular resistance (25 +/- 6% decrease within 90 s of isoproterenol vs. 8 +/- 5% in controls). ACE inhibition did not augment the decrease in resistance but inhibiting both enzymes did so to a lesser extent than inhibiting NEP. These effects cannot be explained by vascular responses secondary to changes of myocardial oxygen consumption. We conclude that NEP and ACE are regulators of myocardial blood flow.
为了确定中性内肽酶（NEP）和激肽酶II（血管紧张素转换酶，ACE）是否影响冠状动脉血流动力学，我们比较了异丙肾上腺素（50mg/kg腹腔注射）给药前后抑制NEP、ACE或两者的效果。我们使用放射性微球在90只麻醉大鼠中测量血流和阻力，这些大鼠接受了NEP抑制剂磷酰胺（2.5mg/kg）、ACE抑制剂卡托普利（2.5mg/kg）、两者联合使用或单独使用赋形剂。在给予异丙肾上腺素之前，抑制NEP、ACE或两者分别使左心室血流量增加48±10（SE）%、33±9%和10±6%，并分别使左心室血管阻力降低26±6%、31±10%和10±6%。给予异丙肾上腺素后，抑制NEP增强了左心室血管阻力的降低（异丙肾上腺素给药后90秒内降低25±6%，而对照组为8±5%）。抑制ACE并没有增强阻力的降低，但同时抑制两种酶的效果比抑制NEP的效果要小。这些效应不能用心肌耗氧量变化继发的血管反应来解释。我们得出结论，NEP和ACE是心肌血流的调节因子。
