Huberdeau D, Barabé J
Département de pharmacologie, faculté de médecine, université de Sherbrooke, Québec, Canada.
Arch Mal Coeur Vaiss. 1990 Jul;83(8):1321-4.
This study was undertaken to verify the activity of plasma kininases in hypertension. Male Wistar rats (WIS) were used and three models of experimental hypertension were studied: spontaneously hypertensive rats (SHR), renal hypertensive rats, made according to the method of Goldblatt, DOCA-salt hypertensive rats. Normal Wistar rats, nephrectomized rats and sodium-loaded rats were used as control groups. Plasma from these animals was used to evaluate the kininase activities: kininase II activity (KII) was measured by the hydrolysis of hippuryl-L-histidyl-L-leucine (HHL); kininase I activity (KI) was measured by the hydrolysis of hippuryl-L-arginine (HLA) (CN1 activity) and of hippuryl-L-lysine (HLL) (CN2 activity). The three enzyme activities were characterized by their kinetic constants and the inhibitory pattern of various inhibitors. In normal WIS rats, hydrolysis of HHL proceeds with a Km of 2.55 +/- 0.22 mM and at a Vmax of 0.357 +/- 0.017 mumol/min/ml; the enzyme is inhibited by EDTA, 0-phenanthroline and captopril. HLA has a Km of 6.93 +/- 0.32 mM and a Vmax of 0.748 +/- 0.019 mumol/min/ml while the Km and Vmax values of HLL are 35.8 +/- 1.52 mM and 13.11 +/- 0.40 mumol/min/ml. The hydrolysis of both substrates is inhibited by EDTA, 0-phenanthroline and MERGETPA. KII activity is decreased in WKY and SHR rats (Vmax = 0.241 +/- 0.014 and 0.262 +/- 0.011 mumol/min/ml, respectively). In renal hypertensive rats and DOCA-salt hypertensive rats, the KII activity remained unchanged. CN1 activity was increased in 1K, 1C hypertensive animals (Vmax = 0.866 +/- 0.221 mumol/min/ml) and in DOCA-salt hypertensive rats (Vmax = 1.119 +/- 0.049 mumol/min/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在验证高血压患者血浆激肽酶的活性。选用雄性Wistar大鼠（WIS），研究了三种实验性高血压模型：自发性高血压大鼠（SHR）、按照戈德布拉特方法制作的肾性高血压大鼠、去氧皮质酮-盐性高血压大鼠。正常Wistar大鼠、肾切除大鼠和高钠负荷大鼠作为对照组。用这些动物的血浆评估激肽酶活性：通过马尿酸-L-组氨酸-L-亮氨酸（HHL）的水解测定激肽酶II活性（KII）；通过马尿酸-L-精氨酸（HLA）（CN1活性）和马尿酸-L-赖氨酸（HLL）（CN2活性）的水解测定激肽酶I活性（KI）。通过其动力学常数和各种抑制剂的抑制模式对这三种酶活性进行表征。在正常WIS大鼠中，HHL的水解以2.55±0.22 mM的Km和0.357±0.017 μmol/min/ml的Vmax进行；该酶被EDTA、邻菲罗啉和卡托普利抑制。HLA的Km为6.93±0.32 mM，Vmax为0.748±0.019 μmol/min/ml，而HLL的Km和Vmax值分别为35.8±1.52 mM和13.11±0.40 μmol/min/ml。两种底物的水解均被EDTA、邻菲罗啉和MERGETPA抑制。WKY和SHR大鼠的KII活性降低（Vmax分别为0.241±0.014和0.262±0.011 μmol/min/ml）。在肾性高血压大鼠和去氧皮质酮-盐性高血压大鼠中，KII活性保持不变。CN1活性在1K、1C高血压动物（Vmax = 0.866±0.221 μmol/min/ml）和去氧皮质酮-盐性高血压大鼠（Vmax = 1.119±0.049 μmol/min/ml）中升高。（摘要截断于250字）
