Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats
Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive rats
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DOI：
10.1161/01.atv.17.6.1152
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发表时间：
1997-06-01
影响因子：
8.7
通讯作者：
Safar, ME
中科院分区：
文献类型：
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作者：
Benetos, A;Lacolley, P;Safar, ME
我们以前已经证明，长期的血管紧张素转换酶（ACE）抑制剂防止自发性高血压大鼠（SHR）主动脉胶原蛋白的增加。与血压降低无关。最近，我们报道了ACE抑制剂在预防主动脉胶原积聚中的作用与抑制血管紧张素II对血管紧张素II 1型受体的作用有关。醛固酮的合成主要由血管紧张素II通过1型受体刺激来调节，已知其在不同的实验模型中促进心脏纤维化。本研究的目的是确定是否抑制醛固酮的形成能够防止自发性高血压大鼠的主动脉纤维化。为此目的，我们比较了4个月的治疗与醛固酮拮抗剂螺内酯与ACE抑制剂喹那普利在4周龄SHR。对照SHR和Wistar-Kyoto（WKY）大鼠接受安慰剂相同的时间段。在治疗结束时，在清醒的SHR与WKY对照组中，喹那普利完全防止了高血压的发展，而螺内酯仅产生轻微但显著的血压降低。ACE抑制剂可显著预防主动脉肥大，但螺内酯不能。相反，喹那普利和安体舒通完全阻止了主动脉胶原蛋白的积聚。在后一种情况下，胶原蛋白密度显著低于WKY对照。这些结果表明，在SHR，螺内酯可以显着防止主动脉纤维化的存在下，一个非常轻微的抗高血压作用。这表明，ACE抑制或1型受体拮抗剂诱导的预防主动脉胶原积累至少部分与醛固酮抑制有关。
We have previously shown that long-term angiotensin-converting enzyme (ACE) inhibition prevents the increase in aortic collagen in spontaneously hypertensive rats (SHRs). independent of blood pressure reduction. More recently, we reported that the effects of ACE inhibition in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type 1 receptors. Aldosterone, the synthesis of which is mainly modulated by angiotensin II through type 1 receptor stimulation, is known to promote cardiac fibrosis in different experimental models. The aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in SHRs. For this purpose, we compared the effects of a 4-month treatment with the aldosterone antagonist spironolactone with the ACE inhibitor quinapril in 4-week-old SHRs. Control SHRs and Wistar-Kyoto (WKY) rats received placebo for the same period of time. At the end of treatment, in conscious SHRs vs WKY controls, quinapril completely prevented the development of hypertension, whereas spironolactone produced only a slight but significant reduction in blood pressure. Aortic hypertrophy was significantly prevented by ACE inhibition but not by spironolactone. On the contrary, aortic collagen accumulation was completely prevented by both quinapril and spironolactone. In the latter case, collagen density was significantly below that of WKY controls. These results show that in SHRs, spironolactone can markedly prevent aortic fibrosis in the presence of a very slight antihypertensive effect. It is suggested that ACE inhibition or type 1 receptor antagonist-induced prevention of aortic collagen accumulation is at least partially related to aldosterone inhibition.