Role of macula densa neuronal nitric oxide synthase in renal diseases
Role of macula densa neuronal nitric oxide synthase in renal diseases
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DOI：
10.1007/s00795-006-0310-2
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发表时间：
2006-03
影响因子：
1.8
通讯作者：
A. Tojo;M. Onozato;T. Fujita
中科院分区：
文献类型：
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作者：
A. Tojo;M. Onozato;T. Fujita
致密斑细胞通过调节输入小动脉血管张力，在调节肾小球血流和肾小球滤过中起重要作用。致密斑神经元型一氧化氮合酶（nNOS）产生的一氧化氮可扩张传入小动脉。致密斑nNOS对肾素分泌很重要，其表达受饮食盐、肾血管紧张素II、细胞内pH和其他因素的调节。在盐敏感性高血压中，nNOS受到抑制，而在SHR或糖尿病早期，nNOS在致密斑沿着NADPH氧化酶增加，这限制了NO的生物利用度。ACEI、潘生丁、α1受体阻滞剂、低盐饮食或碳酸氢钠可通过增强致密斑nNOS来预防高血压、糖尿病和高脂血症引起的肾损害。碳酸氢钠是一种安全且临床可用的致密斑nNOS增强剂，可增加肾小球血流量并防止放射造影剂肾病和慢性肾衰竭中GFR降低。总之，增强致密斑中的nNOS可以是预防肾功能降低的有希望的策略。
Macula densa cells have an important role in the regulation of glomerular blood flow and glomerular filtration by its regulation of afferent arteriolar vascular tone. Nitric oxide derived from neuronal nitric oxide synthase (nNOS) in macula densa can dilate afferent arterioles. Macula densa nNOS is important for renin secretion, and its expression is regulated by dietary salt, renal angiotensin II, intracellular pH, and other factors. In salt-sensitive hypertension, nNOS is suppressed, whereas in SHR or in the early phase of diabetes, nNOS is increased in macula densa along with NADPH oxidase, which limits NO bioavailability. Renal damage induced by hypertension, diabetes, and hyperlipidemia could be prevented by enhancement of nNOS in macula densa with ACEI, dipyridamole, α1-receptor blocker, a low-salt diet, or sodium bicarbonate. Sodium bicarbonate is a safe and clinically available enhancer of nNOS in macula densa that increases glomerular blood flow and prevents the reduction of GFR in radiocontrast nephropathy and chronic renal failure. In conclusion, the enhancement of nNOS in the macula densa can be a promising strategy to prevent reduction of renal function.