Schmetterer L, Findl O, Fasching P, Ferber W, Strenn K, Breiteneder H, Adam H, Eichler H G, Wolzt M
Department of Clinical Pharmacology, Vienna University School of Medicine, Austria.
Diabetes. 1997 Apr;46(4):653-8. doi: 10.2337/diab.46.4.653.
Endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disorders such as diabetic retinopathy. We hypothesized that either local endogenous nitric oxide (NO) synthesis or local reactivity to endogenous NO might be impaired in patients with IDDM and that this may contribute to the development of diabetic retinopathy. Ten otherwise healthy patients with long-standing IDDM and ten healthy control subjects were studied according to an open randomized two-way cross-over design. Subjects received intravenous infusions of either N(G)-monomethyl-L-arginine, an inhibitor of NO-synthase, or L-arginine, the precursor of NO synthesis, on two separate study days. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine decreased fundus pulsations and blood flow velocity in the ophthalmic artery and increased blood pressure in healthy subjects. The responses to NO-synthase inhibition were significantly less in diabetic subjects. In contrast, L-arginine caused a comparable increase in fundus pulsations and decrease in blood pressure in both cohorts. These results indicate that systemic and ocular hemodynamic reactivity to NO-synthase inhibition is reduced in patients with long-standing IDDM, compared with healthy control subjects. Thus, this study indicates that either NO-synthase activity is increased or NO sensitivity is decreased in patients with IDDM and supports the concept of an involvement of the L-arginine-NO system in the pathophysiology of diabetic retinopathy.
内皮功能障碍与糖尿病性血管疾病（如糖尿病视网膜病变）的发病机制有关。我们推测，胰岛素依赖型糖尿病（IDDM）患者的局部内源性一氧化氮（NO）合成或对内源性NO的局部反应性可能受损，这可能导致糖尿病视网膜病变的发生。根据开放随机双向交叉设计，对10名患有长期IDDM的健康患者和10名健康对照者进行了研究。在两个不同的研究日，受试者分别接受静脉输注NO合酶抑制剂N(G)-单甲基-L-精氨酸或NO合成前体L-精氨酸。通过激光干涉测量眼底搏动和多普勒超声测量眼动脉血流速度来评估眼部血流动力学。N(G)-单甲基-L-精氨酸降低了健康受试者的眼底搏动和眼动脉血流速度，并升高了血压。糖尿病患者对NO合酶抑制的反应明显较小。相比之下，L-精氨酸在两个队列中引起了类似的眼底搏动增加和血压降低。这些结果表明，与健康对照者相比，长期IDDM患者对NO合酶抑制的全身和眼部血流动力学反应性降低。因此，本研究表明IDDM患者的NO合酶活性增加或NO敏感性降低，并支持L-精氨酸-NO系统参与糖尿病视网膜病变病理生理学的概念。
