螺内酯联合依那普利治疗对高血压患者胶原更新和血管阻力的影响

Chronic effects of spironolactone in conjunction with an angiotensin-converting enzyme inhibitor enalapril on circulating procollagen marker PⅢNP and vascular resistance in patients with essential hypertension

目的动脉壁细胞外基质的合成和降解紊乱是动脉粥样硬化过程的主要特征。本研究观察3种抗高血压方案下,达到同等血压控制后,循环前胶原更新标志物——Ⅲ型胶原氨基端肽(PⅢNP)的改变和血管阻力的改变。方法轻中度原发性高血压患者130例,随机分为三组,依那普利+螺内酯组(A组,44例,螺内酯20mg/d)、依那普利组(B组,43例)、非直接肾素-血管紧张素-醛固酮系统干预治疗组(C组,43例,β受体阻断剂或钙拮抗剂),观察1年,目标血压<130/80mmHg(1mmHg=0.133kPa)。比较三种治疗方案对心肌胶原更新和外周血管阻力的影响。结果各组均同等有效控制血压,在此前提下,减低血清PⅢNP的疗效[A组(2.3±0.2)μg/L比(3.8±0.2)μg/L,P<0.05;B组(3.4±0.3)μg/L比(3.7±0.3)μg/L,P>0.05;C组(3.9±2.0)μg/L比(3.2±1.5)μg/L,P<0.05]和减低血管阻力[A组(1064.3±158.6)dyn.s-1.cm-5比(1358.3±212.5)dyn.s-1.cm-5;B组(1200.8±298.7)dyn.s-1.cm-5比(1394.0±181.0)dyn.s-1.cm-5;C组(1205.1±206.4)dyn.s-1.cm-5比(1579.9±574.7)dyn.s-1.cm-5,P均<0.05],治疗效果A组优于B组,A、B两组均优于C组。结论螺内酯联合依那普利治疗比单纯依那普利治疗更好地减低血清PⅢNP,使心血管系统间质胶原沉积明显减低,并使血管阻力和顺应性改善,而且该作用不依赖于血压下降。两组均优于非直接肾素-血管紧张素-醛固酮系统干预治疗。

Objective Disturbances of the synthesis and breakdown of the extracellular matrix of arterial walls have emerged as key features of the atherosclerotic process. We observed the changes of circulating procollagen marker for type Ⅲ collagen turnover rate, the N-terminal propeptide P Ⅲ NP and vascular resistance in hypertensive patients treated with various antihypertensive regimens. Method A total of 130 light to moderate hypertensive patients were randomly assigned to receive enalapril （group B, n = 43 ） , enalapril ＋ spirolactone （ 20 mg/d, group A, n = 44 ） and anti-hypertensive drugs not directly affecting RAAS （ calcium antagonist, beta-blocker, group C, n = 43 ） for 1 year. Target blood pressure is 〈 130/80 mm Hg. Results Target blood pressure was reached in all treated patients and was similar among various groups. Under the same blood pressure controlling precondition, serum P m NP were similar at baseline among various groups and remained unchanged in group B [ （ 3.4 ± 0. 3 ） μg/L vs. （ 3.7 ± 0. 3 ）μg/ L, P 〉 0. 05 ] and significantly decreased in group A [ （ 2. 3 ± 0. 2 ） p.g/L vs. （ 3.8 ± 0. 2 ） p.g/L, P 〈 0. 05 ] while significantly increased in group C [ （ 3.9 ± 2.0 ） μg/L vs. （ 3.2 ± 1.5 ） μg/L, P 〈 0. 05 ]. Vascular resistance was similar among groups before therapy and all significantly decreased after 1 year antihypertensive therapy and the decrease was more significant in group A [ （ 1064.3 ± 158.6） dyn·s^-1·cm^-5 ] than that in group B [ （ 1200. 8 ±298.7） dyn·s^-1·cm^-5 ] and group C [ （ 1205. 1 ±206. 4） dyn dyn·s^-1·cm^-5]. Conclusion Spironolactone in conjunction with enalapril is a more favorable antihypertensive regimen in decreasing PⅢ NP and improving vascular resistance than enalapril alone or antihypertensive drug regimens not directly affecting RAAS.