Omland T, Johnson W, Gordon M B, Creager M A
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2248-54. doi: 10.1152/ajpheart.2001.280.5.H2248.
We examined whether physiological stimulation of the endogenous renin-angiotensin system results in impaired endothelium-dependent vasodilatation in forearm resistance vessels of healthy subjects and whether this impairment can be prevented by angiotensin II type 1 receptor blockade. A low-sodium diet was administered to 27 volunteers who were randomized to concomitant treatment with losartan (100 mg once daily) or matched placebo in a double-blind fashion. Forearm blood flow was assessed by venous occlusion plethysmography at baseline and after 5 days. Endothelium-dependent and -independent vasodilation was assessed by intra-arterial infusion of methacholine and verapamil, respectively. The low-sodium diet resulted in significantly decreased urine sodium excretion (placebo: 146 +/- 64 vs. 10 +/- 9 meq/24 h, P < 0.001; losartan: 141 +/- 56 vs. 14 +/- 14 meq/24 h, P < 0.001) and increased plasma renin activity (placebo: 1.0 +/- 0.5 vs. 5.0 +/- 2.5 ng x ml(-1) x h(-1), P < 0.001; losartan: 3.8 +/- 7.2 vs. 19.1 +/- 11.2 ng x ml(-1) x h(-1), P = 0.006) in both the losartan and placebo groups. With the baseline study as the reference, the diet intervention was not associated with any significant change in endothelium-dependent vasodilation to methacholine in either the placebo (P = 0.74) or losartan (P = 0.40) group. We conclude that short-term physiological stimulation of the renin-angiotensin system does not cause clinically significant endothelial dysfunction. Losartan did not influence endothelium-dependent vasodilation in humans with a stimulated renin-angiotensin system.
我们研究了内源性肾素 - 血管紧张素系统的生理刺激是否会导致健康受试者前臂阻力血管中内皮依赖性血管舒张功能受损，以及这种损伤是否可通过1型血管紧张素II受体阻断来预防。对27名志愿者给予低钠饮食，他们被随机双盲分为同时接受氯沙坦（每日100毫克）或匹配安慰剂治疗。在基线和5天后通过静脉阻塞体积描记法评估前臂血流量。分别通过动脉内注射乙酰甲胆碱和维拉帕米评估内皮依赖性和非依赖性血管舒张。低钠饮食导致氯沙坦组和安慰剂组的尿钠排泄显著减少（安慰剂组：146±64对10±9毫当量/24小时，P<0.001；氯沙坦组：141±56对14±14毫当量/24小时，P<0.001），血浆肾素活性增加（安慰剂组：1.0±0.5对5.0±2.5纳克·毫升⁻¹·小时⁻¹，P<0.001；氯沙坦组：3.8±7.2对19.1±11.2纳克·毫升⁻¹·小时⁻¹，P = 0.006）。以基线研究为参照，饮食干预在安慰剂组（P = 0.74）或氯沙坦组（P = 0.40）中均未引起乙酰甲胆碱诱导的内皮依赖性血管舒张的任何显著变化。我们得出结论，肾素 - 血管紧张素系统的短期生理刺激不会导致具有临床意义的内皮功能障碍。氯沙坦对肾素 - 血管紧张素系统受刺激的人类的内皮依赖性血管舒张没有影响。
