Swaminathan K, Davies J, George J, Rajendra N S, Morris A D, Struthers A D
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
Diabetologia. 2008 May;51(5):762-8. doi: 10.1007/s00125-008-0972-5. Epub 2008 Mar 18.
AIMS/HYPOTHESIS: Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones.
We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography.
There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol.
CONCLUSIONS/INTERPRETATION: Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.
目的/假设:醛固酮拮抗剂可改善慢性心力衰竭患者的内皮功能(并降低死亡率)。目前尚不清楚在其他高危人群(如糖尿病和高血压患者)中是否会出现类似效果。因此,我们评估了醛固酮阻断对2型糖尿病且血压控制不佳的高血压患者的全面影响,重点关注血压、内皮功能、血糖控制和关键激素。
我们对50例2型糖尿病且接受治疗但血压控制不佳的患者进行了一项随机、安慰剂对照、双盲、交叉研究,比较螺内酯与安慰剂的效果。通过标准的前臂静脉阻塞体积描记法评估患者的内皮功能。
尽管收缩压和舒张压显著降低,但乙酰胆碱诱导的内皮依赖性血管舒张功能并无显著改善。然而,螺内酯显著恶化了血糖控制、血浆血管紧张素II和皮质醇水平。
结论/解读:在标准治疗下,螺内酯对2型糖尿病且血压控制不佳的患者具有显著的降压效果,但并未改善该组患者的血管内皮功能。我们推测,螺内酯诱导的血压降低改善内皮功能的任何趋势,都被其恶化血糖控制以及增加血管紧张素II甚至可能增加皮质醇水平的趋势所抵消。