Schiffrin E L, Garcia R, Gutkowska J, Boucher R, Genest J
Can J Physiol Pharmacol. 1981 Aug;59(8):864-71. doi: 10.1139/y81-129.
Tonin was injected intravenously to normal rats without effect on blood pressure. Twenty-four hours after bilateral nephrectomy, tonin produced a dose-dependent pressor effect in rats which was abolished by the angiotensin antagonist [Sar1-Ala8]-angiotensin II. Vascular response to angiotensin II was slightly increased after nephrectomy. Plasma angiotensin II increased significantly after injection of tonin and disappeared biexponentially with a half-life of less than 1 min for the fast component and 9 min for the slow component. The change in plasma angiotensin II correlated with the elevation in mean blood pressure. No difference in inhibitory power of plasma on tonin activity could be shown between intact and nephrectomized rats. In vitro, the initial velocity of generation of angiotensin II by tonin acting on plasma increased after addition of semipurified rat renin substrate and was significantly greater in plasma of nephrectomized rats. In nephrectomized rabbits, but not in intact ones, a dose-dependent pressor effect was produced by tonin. These data demonstrate the in vivo production of angiotensin II by tonin in an animal model with elevated substrate levels. Together with the in vitro data, these results suggest a role for substrate concentration in the expression of tonin enzymatic activity in vivo.
向正常大鼠静脉注射托宁，对血压无影响。双侧肾切除24小时后，托宁在大鼠中产生剂量依赖性升压作用，该作用可被血管紧张素拮抗剂[Sar1 - Ala8]-血管紧张素II消除。肾切除后，血管对血管紧张素II的反应略有增加。注射托宁后，血浆血管紧张素II显著升高，并呈双指数消失，快速成分的半衰期小于1分钟，慢速成分的半衰期为9分钟。血浆血管紧张素II的变化与平均血压升高相关。完整大鼠和肾切除大鼠之间，血浆对托宁活性的抑制能力无差异。在体外，添加半纯化大鼠肾素底物后，托宁作用于血浆生成血管紧张素II的初始速度增加，且在肾切除大鼠的血浆中显著更高。在肾切除的兔中，托宁可产生剂量依赖性升压作用，但在完整兔中则不然。这些数据证明了在底物水平升高的动物模型中，托宁在体内可生成血管紧张素II。结合体外数据，这些结果提示底物浓度在体内托宁酶活性表达中起作用。
