Komers Radko, Simkova Renata, Kazdova Ludmila, Ruzickova Jana, Pelikanova Terezie
Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
J Renin Angiotensin Aldosterone Syst. 2004 Mar;5(1):33-8. doi: 10.3317/jraas.2004.006.
Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve endothelial function in Type 1 diabetes. However, the potential of ACE inhibitors (ACE-I) to enhance the haemodynamic effects of L-arginine (L-arg), the precursor of nitric oxide (NO), has not been evaluated. Furthermore, angiotensin receptor blockers (ARBs), another group of inhibitors of the renin-angiotensin system (RAS), have not been studied in this context.
Using a randomised, crossover design, the acute effects of L-arg (200 mg/kg) on blood pressure (BP) and renal haemodynamics were determined in uncomplicated Type 1 diabetic patients before and after three weeks of treatment with the ACE-I ramipril (5 mg/day) or the ARB losartan (50 mg/day).
L-arg alone did not influence BP or renal haemodynamics. BP responses to L-arg were not modulated by ACE-I or ARB. In contrast to the systemic responses, L-arg induced significant renal vasodilation after treatment with ramipril (p<0.05). Unlike ramipril, losartan did not modulate renal haemodynamic responses to L-arg. L-arg administration was paralleled by increments in plasma L-citrulline levels, determined as a measure of L-arg-induced systemic NO production. These responses were not influenced by RAS inhibitors. No changes in other indicators of the systemic and renal NO production, such as plasma and urinary nitrates/nitrites, were detected in response to L-arg alone or after treatment with RAS inhibitors.
ACE-Is have greater potential than ARBs to enhance L-arg effects in the kidney in uncomplicated Type 1 diabetes. Neither RAS inhibitor influenced the systemic effects of L-arg. The lack of changes in renal NO indicators parallelling the haemodynamic responses, suggests that the effects of ACE-I on L-arg-induced renal haemodynamic changes could be also attributable to NO-independent mechanisms.
血管紧张素转换酶（ACE）抑制剂已被证明可改善1型糖尿病患者的内皮功能。然而，ACE抑制剂（ACE-I）增强一氧化氮（NO）前体L-精氨酸（L-arg）血流动力学效应的潜力尚未得到评估。此外，肾素-血管紧张素系统（RAS）的另一类抑制剂——血管紧张素受体阻滞剂（ARBs），在此方面尚未得到研究。
采用随机交叉设计，在未合并并发症的1型糖尿病患者中，测定L-arg（200mg/kg）对血压（BP）和肾血流动力学的急性影响，测定在使用ACE-I雷米普利（5mg/天）或ARB氯沙坦（50mg/天）治疗三周前后进行。
单独使用L-arg不影响BP或肾血流动力学。ACE-I或ARB未调节对L-arg的BP反应。与全身反应不同，雷米普利治疗后L-arg诱导显著的肾血管舒张（p<0.05）。与雷米普利不同，氯沙坦未调节对L-arg的肾血流动力学反应。给予L-arg后血浆L-瓜氨酸水平升高，其作为L-arg诱导的全身NO生成的指标。这些反应不受RAS抑制剂影响。单独给予L-arg或RAS抑制剂治疗后，未检测到全身和肾NO生成的其他指标如血浆和尿硝酸盐/亚硝酸盐的变化。
在未合并并发症的1型糖尿病中，ACE-I比ARBs在增强L-arg对肾脏的作用方面具有更大潜力。两种RAS抑制剂均未影响L-arg的全身作用。肾NO指标变化与血流动力学反应缺乏相关性，提示ACE-I对L-arg诱导的肾血流动力学变化的作用也可能归因于非NO依赖机制。
