Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease
Endothelial dysfunction and reduced nitric oxide in resistance arteries in autosomal-dominant polycystic kidney disease
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DOI：
10.1046/j.1523-1755.2003.00236.x
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发表时间：
2003-10-01
影响因子：
19.6
通讯作者：
Strandgaard, S
中科院分区：
文献类型：
--
作者：
Wang, D;Iversen, J;Strandgaard, S
背景常染色体显性多囊肾病（ADPKD）患者存在内皮依赖性舒张功能（EDR）缺陷。我们研究了内皮功能障碍和一氧化氮的产生在高血压和慢性肾功能不全（CRI）的ADPKD的关系。我们比较了10例正常人、对照组ADPKD和原发性高血压患者皮下阻力血管中乙酰胆碱（ACh）诱导的EDR、3-吗啉代糖醛酮亚胺（SIN-1）诱导的内皮非依赖性舒张（EIDR）和组成型一氧化氮合酶（cNOS）活性以及血浆中NO2-/NO3-（NOX）水平和排泄量。EDR在血压正常的ADPKD组（N = 9）中显著降低，但在高血压ADPKD组（N = 6）、CRI组（N = 5）和原发性高血压组（N = 9）中更严重。在所有ADPKD患者组和原发性高血压患者组中，L-精氨酸增加EDR和L-G-硝基-L-精氨酸甲酯（L-NAME）降低EDR的作用均消失，除了L-NAME对血压正常的ADPKD有适度的影响。EIDR在整个过程中未受损。血管cNOS活性和肾脏NOX排泄在所有类型的ADPKD患者中均显著降低，尤其是在高血压患者中。ADPKD患者阻力血管中的EDR即使在没有高血压或CRI的情况下也会受损，但随着高血压的发展而变得更加明显。ADPKD患者cNOS活性降低导致一氧化氮生成缺陷。ADPKD患者内皮功能障碍和cNOS活性受损可能易患高血压，其发生伴随EDR进一步急剧恶化。
Background. Patients with autosomal-dominant polycystic kidney disease ( ADPKD) have defective endothelium-dependent relaxation (EDR). We investigated the relationship between endothelial dysfunction and nitric oxide generation in hypertension and chronic renal insufficiency (CRI) in ADPKD.Methods. We contrasted acetylcholine (ACh)-induced EDR, 3-morphollinosydnonimine (SIN-1)-induced endothelium-independent relaxation (EIDR) and constitutive nitric oxide synthase (cNOS) activity in subcutaneous resistance vessels and plasma levels and excretion of NO2-/NO3- (NOX) in normal, control (N = 10) patients with ADPKD or essential hypertension.Results. EDR was decreased significantly in normotensive ADPKD (N = 9), but more severely in hypertensive ADPKD (N = 6), or those with CRI (N = 5) and in essential hypertension (N = 9). The increases in EDR with L-arginine and decreases with L-G-nitro-L-arginine methyl ester (L-NAME) were lost in all groups of patients with ADPKD and in essential hypertension except for a modest effect of L-NAME in normotensive ADPKD. EIDR was unimpaired throughout. Vascular cNOS activity and renal NOX excretion were reduced profoundly in patients with all categories of ADPKD and especially in those with hypertension.Conclusion. EDR in resistance vessels from patients with ADPKD is impaired even in the absence of hypertension or CRI, but becomes more marked as hypertension develops. Patients with ADPKD have defective nitric oxide generation from diminished cNOS activity. Endothelial dysfunction and impaired cNOS activity in ADPKD may predispose to hypertension whose occurrence is accompanied by a further sharp deterioration in EDR.