Abstract

The hypotensive effect of arginase inhibition [1] can be achieved experimentally in two ways: by increasing the nitric oxide (NO) concentration that causes vasorelaxation, and/or by decreasing the circulating fluid volume. The first way occurs with an increase in the availability of the NO synthase (NOS) substrate arginine (ARG), while the second can be implemented with an increase in diuresis. To define more exactly the ways in which arginase affects arterial blood pressure (BP) regulation, we analyzed the metabolic characteristics of the amino acid L-arginine in hypertensive (ISIAH strain) and normotensive (WAG strain) rats under the inhibition of arginase activity by L-norvaline. Concentrations of ARG and its metabolite ornithine were measured in blood, urine, and kidney tissue homogenates using high-performance liquid chromatography with the separation on a reversed-phase sorbent and fluorescence detection. Norvaline was administered intraperitoneally (i.p.) once a day at a dose of 30 mg/kg for 7 days. Norvaline caused no significant changes in the blood concentration of amino acids in both normotensive and hypertensive rats. After norvaline administration, the urine ARG concentration in normotensive rats remained intact, but increased twofold in hypertensive rats. Daily ARG excretion in norvaline-treated normotensive rats increased quite insignificantly, but in hypertensive rats increased under the same conditions almost threefold, with diuresis being increased in hypertensive rats only. Under the effect of norvaline, the ARG content per 1 g of kidney weight was intact in normotensive rats but increased almost twofold in hypertensive rats. Our data indicate that arginase inhibition by norvaline had a stronger hypotensive effect on hypertensive rather than normotensive rats. At the same time, in normotensive rats, the hypotensive effect of norvaline may be provided by the NO system, while in hypertensive rats, it seems to be realized through enhanced diuresis.

中文翻译：

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正缬氨酸抑制精氨酸酶对高血压大鼠精氨酸代谢的影响

摘要

精氨酸酶抑制的降压作用 [1] 可以通过两种方式通过实验实现：通过增加导致血管舒张的一氧化氮 (NO) 浓度，和/或通过减少循环液量。第一种方式随着一氧化氮合酶 (NOS) 底物精氨酸 (ARG) 的可用性增加而发生，而第二种方式可以通过增加利尿作用来实现。为了更准确地定义精氨酸酶影响动脉血压 (BP) 调节的方式，我们分析了在精氨酸酶活性抑制下，高血压（ISIAH 品系）和血压正常（WAG 品系）大鼠的氨基酸 L-精氨酸的代谢特征。 L-正缬氨酸。ARG 及其代谢物鸟氨酸的浓度在血液、尿液、和肾组织匀浆使用高效液相色谱分离，反相吸附剂和荧光检测。正缬氨酸以 30 mg/kg 的剂量每天一次腹膜内 (ip) 给药，持续 7 天。正缬氨酸对血压正常和高血压大鼠的血液氨基酸浓度均无显着影响。服用正缬氨酸后，血压正常大鼠的尿 ARG 浓度保持不变，但高血压大鼠的尿 ARG 浓度增加了两倍。正缬氨酸治疗的血压正常大鼠的每日 ARG 排泄量增加相当微不足道，但在相同条件下，高血压大鼠的 ARG 排泄量增加了近三倍，只有高血压大鼠的利尿作用增加。在正缬氨酸的作用下，每 1 g 肾脏重量的 ARG 含量在血压正常的大鼠中是完整的，但在高血压大鼠中几乎增加了两倍。我们的数据表明，正缬氨酸对精氨酸酶的抑制对高血压而非血压正常的大鼠具有更强的降压作用。同时，在血压正常的大鼠中，正缬氨酸的降压作用可能是由一氧化氮系统提供的，而在高血压大鼠中，它似乎是通过增强利尿作用来实现的。