Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs
Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs
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DOI：
10.1152/ajpheart.1997.273.2.h961
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发表时间：
1997-08-01
影响因子：
4.8
通讯作者：
Oparil, S
中科院分区：
文献类型：
--
作者：
DellItalia, LJ;Balcells, E;Oparil, S
我们测试了血管紧张素转换酶(ACE)抑制剂治疗预防慢性二尖瓣反流(MR)犬容量超负荷肥厚的假设。7只成年杂种犬口服雷米普利(R；10 mg，2次/d)4mo，与11只在MR诱导后4mo不服用R(N)的犬进行比较。电影磁共振成像显示，R-MR组和N-MR组的左心室质量分别增加[80+/-4(SE)至108+/-7g，P<；0.01]和N-MR犬(92+/-7至112+/-8g，P<；0.001)。R-MR和N-MR犬左室肌细胞长度分别为203+/-6和177+/-10微米，明显大于正常犬(144+/-4微米，P<0.05)。扫描电子显微镜观察显示，R-MR和N-MR均有明显的胶原编织结构丢失。与正常犬相比，R-MR和N-MR的左心室血管紧张素转换酶和糜酶活性均显著升高。与N-MR组(72+/-11pg/g)相比，R-MR组(28+/-12pg/g)左心室血管紧张素Ⅱ(Ang II)水平降低至正常组(28+/-4pg/g)。稳态AT(1)受体基因表达水平N-MR较正常犬降低66%(P<；0.001)，R-MR较正常犬增加1.5倍(P<；0.01)。因此，R-MR心脏AT(1)受体的上调可能提供了一种机制，通过这种机制，心脏内正常的Ang II水平可以继续介导左室肥厚。然而，N-MR和R-MR心脏溶解胶原编织的机制可能与容量超负荷的伸展有关。
We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy prevents volume-overload hypertrophy in dogs with chronic mitral regurgitation (MR). Seven adult mongrel dogs receiving ramipril (R; 10 mg orally, twice/day) for 4 mo were compared with 11 dogs receiving no R (N) for 4 mo after induction of MR. Cine-magnetic resonance imaging demonstrated that left ventricular (LV) mass increased in the R-MR dogs [80 +/- 4 (SE) to 108 +/- 7 g, P < 0.01] and in the N-MR dogs (92 +/- 7 to 112 +/- 8 g, P < 0.001). LV myocyte cell length was greater in the R-MR and N-MR dogs (203 +/- 6 and 177 +/- 10 mu m, respectively) than in normal (144 +/- 4 mu m, P < 0.05) dogs. There was significant loss of the collagen weave pattern by scanning electron microscopy in both R-MR and N-MR dogs. LV ACE and chymase activities were significantly elevated in R-MR and N-MR compared with normal dogs. LV angiotensin II (ANG II) levels in the R-MR dogs (28 +/- 12 pg/g) were reduced to levels seen in normal dogs (28 +/- 4 pg/g) compared with N-MR dogs (72 +/- 11 pg/g, P < 0.05). Steady-state AT(1)-receptor mRNA levels decreased 66% in N-MR compared with normal dogs (P < 0.001) and increased 1.5-fold in R-MR compared with normal dogs (P < 0.01). Thus upregulation of the AT(1) receptor in the R-MR hearts may provide a mechanism by which normal intracardiac ANG II levels could continue to mediate LV hypertrophy. However, the mechanism of dissolution collagen weave in both N-MR and R-MR hearts may be related to the stretch of volume overload.