Effects of acute and chronic L-arginine treatment in experimental hyperuricemia
Effects of acute and chronic L-arginine treatment in experimental hyperuricemia
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DOI：
10.1152/ajprenal.00164.2006
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发表时间：
2007-04-01
影响因子：
4.2
通讯作者：
Franco, Martha
中科院分区：
文献类型：
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作者：
Sanchez-Lozada, Laura G.;Tapia, Edilia;Franco, Martha
实验性高尿酸血症(HU)导致肾小球前动脉病变、皮质血管收缩和肾小球高血压。最近，尿酸被证明可以引起内皮功能障碍。因此，我们研究了急性和慢性给予内皮型一氧化氮合酶底物L-精氨酸对HU所致肾血流动力学和血管结构改变的影响。给雄性SD大鼠灌胃氧酸750 mg·kg~(-1)·d~(-1)以诱发HU。为研究精氨酸的急性作用，9只大鼠在显微穿刺术中注射L-精氨酸(L-精氨酸15 mg·kg~(-1)·min~(-1))。为了阐明L精氨酸的慢性作用，在5周的治疗期间，分别评价了OA+1%L-Arg组(n=8)和OA+2.5%L-Arg组(n=6)。8只正常对照组(N)和8只OA大鼠也被研究。通过灌流固定肾脏，并评价传入小动脉的形态。HU大鼠出现上述肾脏功能和结构改变，并抑制尿中NO(2)(-)/NO(3)(-)的排泄。急性刺激一氧化氮(NO)合成显著增加尿NO(2)(-)/NO(3)(-)，降低全身血压，减轻皮质血管收缩，尽管肾小球高血压和传入小动脉损伤显著增加。慢性L-精氨酸剂量的增加与增加尿NO(2)(-)/NO(3)(-)排泄、降低全身高血压和防止皮质血管收缩(2.5%L-精氨酸)有关。此外，这两种剂量都可以预防肾小球高血压和肾小球前动脉病变。因此，在传入小动脉受损的情况下，急性缓解肾血管收缩并不能逆转肾小球高血压，这可能是由于肾小球前自我调节功能受损所致。另一方面，慢性L-精氨酸对小动脉结构的保护作用可能与NO对血管平滑肌细胞增殖的抑制作用有关。
Experimental hyperuricemia (HU) results in preglomerular arteriolopathy, cortical vasoconstriction, and glomerular hypertension. Recently, uric acid has been shown to induce endothelial dysfunction. We therefore studied the effect of acute and chronic administration of L-arginine (a substrate for endothelial nitric oxide synthase) on the renal hemodynamic and vascular structural alterations induced by HU. To induce HU, oxonic acid (OA; 750 mg(.)kg(-1.)day(-1)) was administered in male Sprague-Dawley rats. To study the acute effect of arginine, nine rats received L-arginine (L-Arg; 15 mg(.)kg(-1.)min(-1)) during micropuncture. To elucidate the chronic effect of L-Arg, OA + 1% L-Arg (n = 8) and OA + 2.5% L-Arg (n = 6; drinking water) were evaluated throughout the 5-wk period. Eight normal control (N), and eight OA, rats were also studied. Kidneys were fixed by perfusion and afferent arteriole morphology was evaluated. HU rats developed the renal functional and structural alterations described and had suppressed urinary excretion of NO(2)(-)/NO(3)(-). Acute stimulation of nitric oxide (NO) synthesis markedly increased urinary NO(2)(-)/NO(3)(-), lowered systemic blood pressure, and relieved cortical vasoconstriction despite a significant increment of glomerular hypertension and afferent arteriole damage. Increasing doses of chronic L-Arg were associated with increasing excretion of urinary NO(2)(-)/NO(3)(-), reduction of systemic hypertension, and prevention of cortical vasoconstriction (2.5% L-Arg). In addition, both doses prevented glomerular hypertension and preglomerular arteriolopathy. Thus an acute relief of renal vasoconstriction in the setting of afferent arteriole damage cannot reverse glomerular hypertension, likely due to impairment in preglomerular autoregulation. On the other hand, chronic L-Arg preserved arteriolar structures probably mediated by the antiproliferative effect of NO on vascular smooth muscle cells.