López Bernardo, Salom Miguel García, Arregui Begoña, Valero Fernando, Fenoy Francisco J
Departamento de Fisiología, Facultad de Medicina, Campus Universitario de Espinardo, 30100-Murcia, Spain.
Hypertension. 2003 Dec;42(6):1150-6. doi: 10.1161/01.HYP.0000101968.09376.79. Epub 2003 Nov 3.
Angiotensin II is known to stimulate NADPH oxidase-dependent superoxide (O2-) generation, which may contribute to the acute renal vasoconstrictor and antinatriuretic actions of this peptide. To evaluate this hypothesis, the effects of a superoxide dismutase mimetic (tempol) or a NADPH inhibitor (apocynin) on the angiotensin renal actions were studied. Renal cortical nitric oxide (NO) was measured electrochemically in vivo. Tempol increased sodium excretion and NO levels. Apocynin raised renal blood flow, glomerular filtration rate, sodium excretion, and NO levels. These results indicate the presence of an endogenous NADPH oxidase-dependent O2- generation that may modulate renal function by scavenging NO. Angiotensin II infusion reduced renal blood flow, glomerular filtration, sodium excretion, and NO levels in a dose-dependent manner. The angiotensin receptor antagonist valsartan, tempol, or apocynin blunted the angiotensin effects on renal excretion and NO, suggesting that angiotensin receptors stimulation induces the NADPH oxidase-dependent O2- generation that might reduce NO bioavailability. This idea is supported by the finding that angiotensin increased O2- generation in renal homogenates, and this effect was prevented by valsartan, apocynin, or tempol. These results indicate that some of the acute renal effects of angiotensin II may be enhanced by an increased NADPH oxidase-derived O2- production that reduces renal NO bioavailability.
已知血管紧张素II可刺激NADPH氧化酶依赖性超氧阴离子（O2-）生成，这可能有助于该肽的急性肾血管收缩和利钠作用。为了评估这一假设，研究了超氧化物歧化酶模拟物（tempol）或NADPH抑制剂（阿朴吗啡）对血管紧张素肾作用的影响。采用电化学方法在体内测定肾皮质一氧化氮（NO）。Tempol增加了钠排泄和NO水平。阿朴吗啡提高了肾血流量、肾小球滤过率、钠排泄和NO水平。这些结果表明存在内源性NADPH氧化酶依赖性O2-生成，其可能通过清除NO来调节肾功能。血管紧张素II输注以剂量依赖性方式降低了肾血流量、肾小球滤过、钠排泄和NO水平。血管紧张素受体拮抗剂缬沙坦、tempol或阿朴吗啡减弱了血管紧张素对肾排泄和NO的作用，提示血管紧张素受体刺激诱导了NADPH氧化酶依赖性O2-生成，这可能降低NO的生物利用度。血管紧张素增加肾匀浆中O2-生成，而缬沙坦、阿朴吗啡或tempol可阻止这种作用，这一发现支持了这一观点。这些结果表明，血管紧张素II的一些急性肾作用可能因NADPH氧化酶衍生的O2-生成增加而增强，从而降低肾NO的生物利用度。
