Cheetham C, Collis J, O'Driscoll G, Stanton K, Taylor R, Green D
Department of Human Movement and Exercise Science, The University of Western Australia, Royal Perth Hospital, Australia.
J Am Coll Cardiol. 2000 Nov 1;36(5):1461-6. doi: 10.1016/s0735-1097(00)00933-5.
The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM).
Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function.
The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography.
Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed.
Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.
本研究探讨血管紧张素II 1型受体拮抗剂氯沙坦对非胰岛素依赖型糖尿病（NIDDM）患者前臂内皮功能的影响。
依那普利抑制血管紧张素转换酶（ACE）可改善NIDDM患者乙酰胆碱（ACh）依赖的内皮功能。这可能是通过血管紧张素II和1型受体介导的，也可能是由于抑制激肽释放酶II和缓激肽的保留作用。因此，确定1型受体拮抗剂是否能改善内皮功能具有重要意义。
采用双盲安慰剂对照交叉方案，对9例NIDDM患者测定氯沙坦（每日50mg，共4周）对内皮依赖性和非依赖性血管舒张功能的影响。使用应变片体积描记法测量前臂血流量。
氯沙坦可显著降低对三次递增剂量肱动脉内乙酰胆碱的输注臂血管阻力（p<0.05，方差分析）。前臂血流量比值（输注臂与非输注臂血流量之比）也增加（p<0.01）。对硝普钠和单甲基精氨酸的反应无显著变化。
每日服用50mg氯沙坦可改善NIDDM患者阻力血管的内皮依赖性舒张。也就是说，阻断血管紧张素II 1型受体可改善NIDDM患者的内皮功能。ACE抑制的至少一些类似有益作用可能也通过血管紧张素II-1型受体途径介导。在NIDDM患者中，使用1型受体拮抗剂似乎是维持内皮功能的一种合理替代ACE抑制剂的方法。
