The effect of aprotinin (a serine protease inhibitor) on renal function and renin release.
The effect of aprotinin (a serine protease inhibitor) on renal function and renin release.
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DOI：
10.1161/01.hyp.5.6.893
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发表时间：
1983-11
期刊：
影响因子：
8.3
通讯作者：
S. Seto;V. Kher;A. Scicli;W. Beierwaltes;O. Carretero
中科院分区：
文献类型：
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作者：
S. Seto;V. Kher;A. Scicli;W. Beierwaltes;O. Carretero
我们研究了抑肽酶（一种激肽释放酶和其他丝氨酸蛋白酶的可逆抑制剂）对尿激肽释放酶和激肽排泄、肾功能和血流动力学、血压以及血浆肾素活性（PRA）的影响。当以10,000激肽释放酶抑制单位（KIU）/千克的剂量给麻醉大鼠一次性注射抑肽酶，并以1000 KIU/千克/分钟的速度输注60分钟时，尿激肽原酶活性以及免疫反应性激肽释放酶、激肽、钠、钾和水的排泄以及PRA均显著降低。抑肽酶还导致肾血流量（RBF）减少36%（p<0.001），肾小球滤过率（GFR）降低37%（p<0.001），尽管血压和心输出量均未改变。在清醒大鼠中，我们进一步研究了抑肽酶在异丙肾上腺素或呋塞米刺激肾素释放前后对PRA的影响。抑肽酶（5000 KIU/千克一次性注射和1000 KIU/千克/分钟输注60分钟）没有改变基础的或异丙肾上腺素刺激的PRA，但它减弱了呋塞米刺激引起的PRA升高。较高剂量的抑肽酶（20,000 KIU/千克一次性注射和5000 KIU/千克/分钟输注60分钟）显著降低血压，增加血细胞比容和PRA。这些影响可能是由于抑制了丝氨酸蛋白酶，或者是由于这种高度阳离子性质的肽的其他尚未被认识的特性。总之，低剂量的抑肽酶减少了激肽释放酶、激肽、钠和水的排泄。这些减少可能是由于抑制了激肽释放酶和/或其他丝氨酸蛋白酶，或者可能是继发于肾脏血流动力学变化。（摘要截断至250字）
We studied the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, upon urinary kallikrein and kinin excretion, renal function and hemodynamics, blood pressure, and plasma renin activity (PRA). When aprotinin was administered to anesthetized rats at 10,000 KIU/kg as a bolus, and at 1000 KIU/kg/min infusion for 60 minutes, urinary kininogenase activity and immunoreactive kallikrein, kinins, sodium, potassium, and water excretion, and PRA decreased significantly. Aprotinin also caused a 36% decrease (p less than 0.001) in renal blood flow (RBF), and a 37% decrease (p less than 0.001) in glomerular filtration rate (GFR), although neither blood pressure nor cardiac output changed. The effect of aprotinin on PRA was further studied in conscious rats before and after stimulation of renin release by isoproterenol or furosemide. Aprotinin (5,000 KIU/kg bolus and 1000 KIU/kg/min infusion for 60 minutes) did not alter basal or isoproterenol-stimulated PRA, but it blunted the increase in PRA as stimulated by furosemide. Aprotinin at a higher dose (20,000 KIU/kg bolus and 5000 KIU/kg/min infusion for 60 minutes) significantly lowered blood pressure and increased hematocrit and PRA. These effects may be due to inhibition of serine protease(s) or to other as yet unrecognized properties of this peptide resulting from its highly cationic nature. In conclusion, aprotinin at a low dose decreased kallikrein, kinin, sodium, and water excretion. These decreases may be due to the inhibition of kallikrein and/or other serine proteases or may be secondary to the renal hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)