Exogenous L-arginine ameliorates angiotensin II-induced hypertension and renal damage in rats.
Exogenous L-arginine ameliorates angiotensin II-induced hypertension and renal damage in rats.
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DOI：
10.1161/hypertensionaha.108.114298
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发表时间：
2008-12
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影响因子：
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通讯作者：
Mattson DL
中科院分区：
文献类型：
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作者：
Rajapakse NW;De Miguel C;Das S;Mattson DL
进行实验以确定外源性 L-精氨酸是否可以改善血管紧张素 II 诱导的高血压和肾损伤。给大鼠配备长期留置的股静脉和动脉导管，用于输注药物和测量清醒动脉压。连续输注血管紧张素 II（20 ng/kg/min；静脉注射；n=6-9）9 天后，动脉血压从 124±1 mmHg 显着升高至 199±4 mmHg。相比之下，在同时给予 L-精氨酸（300 µg/kg/min；静脉注射；n=7-9）的大鼠中，血管紧张素 II 输注 9 天后动脉压的升高显着减弱了 45%（P = 0.0003）。与施用盐水载体的大鼠相比，施用血管紧张素II的大鼠的肾小球损伤指数显着更高(P<0.001)。联合输注L-精氨酸显着增加血浆硝酸盐/亚硝酸盐浓度（P<0.001），并完全预防血管紧张素II诱导的肾小球损伤（P<0.001）。单独输注血管紧张素II以及联合输注血管紧张素II和L-精氨酸显着增加尿白蛋白排泄。给予血管紧张素 II 加 L-精氨酸的大鼠的蛋白尿可能是由于肾小球内压力增加所致。我们的实验表明，L-精氨酸可以减轻血管紧张素 II 诱导的高血压和相关的肾损伤。后一个观察结果是最令人兴奋的，因为它表明除了降低动脉压之外，增加一氧化氮的生物利用度还可以大大减少高血压引起的肾损伤。
Experiments were performed to determine whether exogenous L-arginine could ameliorate angiotensin II-induced hypertension and renal damage. Rats were instrumented with chronic indwelling femoral venous and arterial catheters for infusions of drugs and measurement of conscious arterial pressure. Arterial blood pressure significantly increased from 124±1 to 199±4 mmHg, following 9 days of continuous infusion of angiotensin II (20 ng/kg/min; i.v; n=6–9). In contrast, the increase in arterial pressure after 9 days of angiotensin II infusion was significantly blunted by 45% (P = 0.0003) in rats co-administered L-arginine (300 µg/kg/min; i.v; n=7–9). The glomerular injury index was significantly greater in rats administered angiotensin II in comparison to rats administered saline vehicle (P<0.001). Co-infusion of L-arginine significantly increased plasma nitrate/nitrite concentrations (P<0.001), and completely prevented angiotensin II-induced glomerular damage (P<0.001). Angiotensin II infusion alone, and combined angiotensin II plus L-arginine infusion significantly increased urinary albumin excretion. Albuminuria in rats administered angiotensin II plus L-arginine is likely to be due to increased intraglomerular pressure. Our experiments demonstrate that L-arginine can blunt angiotensin II induced hypertension and associated renal damage. This latter observation is most exciting as it indicates that increasing nitric oxide bioavailability, in addition to lowering arterial pressure, can greatly reduce hypertension induced renal damage.