Vishwanatha J K, Davis R G, Blumberg S, Gao X P, Rubinstein I
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, USA.
Am J Hypertens. 1998 May;11(5):585-90. doi: 10.1016/s0895-7061(98)00028-4.
The purpose of this study was to determine whether tissue neutral endopeptidase (NEP) 24.11 activity, a membrane-bound metalloenzyme widely distributed in the peripheral circulation that cleaves and inactivates vasodilator peptides, is increased in spontaneously hypertensive hamsters relative to genetically/age-matched normotensive hamsters. Mean arterial pressure and heart rate were 163 +/- 11 mm Hg and 312 +/- 7 beats/min in spontaneously hypertensive hamsters and 99 +/- 3 mm Hg and 302 +/- 10 beats/min in normotensive hamsters, respectively (mean +/- SEM). NEP 24.11 activity is significantly increased in the kidney, cheek pouch, and spinotrapezius muscle, and significantly decreased in the heart and aorta of spontaneously hypertensive hamsters relative to controls (P < .05). Lung and brain NEP 24.11 activity is similar in both groups. Renal NEP 24.11 activity increases and to a similar extent in spontaneously hypertensive and normotensive hamsters as chloride anion concentration in the assay buffer is increased. Substituting citrate for chloride anion significantly attenuates renal NEP 24.11 activity. Taken together, these data indicate that NEP 24.11 activity in spontaneously hypertensive hamsters is increased in two organs that contribute appreciably to peripheral vascular resistance, skeletal muscle, and kidney. We suggest that the spontaneously hypertensive hamster is a suitable model to study the role of skeletal muscle and renal NEP 24.11 in regulating vasomotor tone in essential hypertension.
本研究的目的是确定组织中性内肽酶（NEP）24.11的活性在自发性高血压仓鼠中相对于基因/年龄匹配的正常血压仓鼠是否升高。NEP 24.11是一种膜结合金属酶，广泛分布于外周循环中，可裂解并使血管舒张肽失活。自发性高血压仓鼠的平均动脉压和心率分别为163±11 mmHg和312±7次/分钟，正常血压仓鼠的平均动脉压和心率分别为99±3 mmHg和302±10次/分钟（平均值±标准误）。相对于对照组，自发性高血压仓鼠的肾脏、颊囊和斜方肌中NEP 24.11的活性显著升高，而心脏和主动脉中的活性则显著降低（P<0.05）。两组的肺和脑NEP 24.11活性相似。随着测定缓冲液中氯离子浓度的增加，自发性高血压和正常血压仓鼠的肾脏NEP 24.11活性均增加，且增加程度相似。用柠檬酸盐替代氯离子可显著减弱肾脏NEP 24.11的活性。综上所述，这些数据表明，在对周围血管阻力有显著影响的两个器官——骨骼肌和肾脏中，自发性高血压仓鼠的NEP 24.11活性升高。我们认为，自发性高血压仓鼠是研究骨骼肌和肾脏NEP 24.11在原发性高血压中调节血管舒缩张力作用的合适模型。
