Nongenomic vascular action of aldosterone in the glomerular microcirculation
Nongenomic vascular action of aldosterone in the glomerular microcirculation
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DOI：
10.1097/01.asn.0000083982.74108.54
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发表时间：
2003-09-01
影响因子：
13.6
通讯作者：
Ito, S
中科院分区：
文献类型：
--
作者：
Arima, S;Kohagura, K;Ito, S
在恶性高血压或慢性肾功能衰竭的动物模型中，醛固酮（Aldo）加速高血压、蛋白尿和肾小球硬化。Aldo可能通过升高肾血管阻力和肾小球毛细血管压力来发挥这些有害的肾脏作用。为了测试这种可能性，直接检查了Aldo对传入（Af）和传出（Ef）小动脉的作用（Arts）。检查了添加到浴和管腔中的Aldo对家兔管腔内直径（在最敏感点测量）的影响。阿尔多引起剂量依赖性收缩的两个小动脉具有较高的灵敏度在EF艺术。Aldo的血管收缩作用不受盐皮质激素受体拮抗剂螺内酯的影响，并被膜不可渗透的白蛋白结合的Aldo复制，表明血管收缩作用是非基因组的。用新霉素（一种磷脂酶C的特异性抑制剂）预处理，废除了Aldo在两条小动脉中的血管收缩作用。Aldo对Af-Arts的缩血管作用可被硝苯地平和依福地平抑制，而对Ef-Arts的缩血管作用可被依福地平抑制，但硝苯地平不抑制。结果表明，Aldo引起非基因组血管收缩，激活磷脂酶C与随后的钙动员通过L-或T-型电压依赖性钙通道Af或EF-艺术，分别。这些对肾小球微循环的血管收缩作用可能通过升高肾血管阻力和肾小球毛细血管压力在肾脏疾病的病理生理和进展中起重要作用。
Aldosterone (Aldo) accelerates hypertension, proteinuria, and glomerulosclerosis in animal models of malignant hypertension or chronic renal failure. Aldo may exert these deleterious renal effects by elevating renal vascular resistance and glomerular capillary pressure. To test this possibility, directly examined were the action of Aldo on the afferent (Af) and efferent (Ef) arterioles (Arts). Examined were the effect of Aldo added to both the bath and lumen on the intraluminal diameter (measured at the most responsive point) of rabbits. Aldo caused dose-dependent constriction in both arterioles with a higher sensitivity in Ef-Arts. Vasoconstrictor action of Aldo was not affected by a mineralocorticoid receptor antagonist spironolactone and was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that the vasocon-strictor actions are nongenomic. Pretreatment with neomycin (a specific inhibitor of phospholipase C) abolished the vasoconstrictor action of Aldo in both arterioles. In addition, the vasoconstrictor action of Aldo on Af-Arts was inhibited by both nifedipine and efonidipine, whereas that on Ef-Arts was inhibited by efonidipine but not nifedipine. The results demonstrate that Aldo causes nongenomic vasoconstriction by activating phospholipase C with a subsequent calcium mobilization thorough L- or T-type voltage-dependent calcium channels in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating renal vascular resistance and glomerular capillary pressure.