高血压性心脏病中心肌纤维化的消退：各种降压药物的不同作用

Regression of myocardial fibrosis in hypertensive heart disease: diverse effects of various antihypertensive drugs.

作者信息

Brilla C G

机构信息

Center of Internal Medicine, Division of Cardiology, Philipps University of Marburg, Baldingerstrasse, D-35033, Marburg, Germany.

出版信息

Cardiovasc Res. 2000 May;46(2):324-31. doi: 10.1016/s0008-6363(99)00432-0.

DOI:10.1016/s0008-6363(99)00432-0

PMID:10773237

Abstract

OBJECTIVE

In left ventricular hypertrophy (LVH) due to systemic hypertension, myocardial fibrosis is an important determinant of pathologic hypertrophy. Therefore, it is most relevant to utilize an antihypertensive regimen that permits a regression in myocardial fibrosis along with blood pressure normalization and regression of LVH.

METHODS

To address this issue we examined 60 Sprague-Dawley rats. We treated 16-week-old rats having established LVH and myocardial fibrosis due to 8-week renovascular hypertension (RHT) with either 6 mg/kg/day zofenopril (ZOF), 30 mg/kg/day nifedipine (NIF) or 40 mg/kg/day labetalol (LAB) for 12 weeks. Systolic arterial pressure (SAP, mmHg), left ventricular/body weight ratio (LV/BW, mg/g), and left and right ventricular collagen volume fractions (LVCVF, RVCVF, %) were obtained and compared with age/sex matched untreated rats with RHT and sham-operated controls.

RESULTS

In RHT, SAP was significantly elevated compared with controls (188+/-11 vs. 125+/-5 mmHg; P<0.001) while in each treated group SAP was normalized. LV/BW was significantly increased in RHT (2.61+/-0.12 mg/g; P<0.00001) while in each treated group LVH was completely regressed (P<0.002 vs. untreated RHT) with LV/BW values comparable to controls (1.82+/-0.03 mg/g) irrespective of the utilized antihypertensive agent. In untreated RHT, myocardial fibrosis was present in the left (LVCVF: 12.3+/-1.9%; P<0.0005 vs. 4.5+/-0.2% of controls) and right ventricles (RVCVF: 20.6+/-2.5%; P<0.00005 vs. 8.8+/-0.4% of controls). In rats treated with ZOF or NIF, LVCVF was significantly reduced to 5.6+/-0.4 and 5.4+/-0.6%, respectively (P<0.005 vs. untreated RHT), and RVCVF was decreased as well (ZOF: 11.0+/-0.9%; NIF: 10.4+/-2.4%; P<0.007 vs. untreated RHT) where no significant difference to controls remained. In contrast, treatment with LAB did not affect myocardial fibrosis where LVCVF was 9.3+/-1.3% and RVCVF was 19.8+/-2.8%, i.e., remained significantly elevated compared with controls (P<0.007).

CONCLUSIONS

In rats with renovascular hypertension and hypertensive heart disease that included LVH and fibrosis, equipotent doses of ZOF, NIF, and LAB normalized arterial pressure associated with regression of LVH while only ZOF and NIF were found to regress myocardial fibrosis.

摘要

目的

在因系统性高血压导致的左心室肥厚（LVH）中，心肌纤维化是病理性肥厚的重要决定因素。因此，采用一种能使心肌纤维化消退、同时使血压正常化并使LVH消退的降压方案至关重要。

方法

为解决这一问题，我们研究了60只Sprague-Dawley大鼠。我们用6毫克/千克/天的佐芬普利（ZOF）、30毫克/千克/天的硝苯地平（NIF）或40毫克/千克/天的拉贝洛尔（LAB）对因8周肾血管性高血压（RHT）而出现LVH和心肌纤维化的16周龄大鼠进行治疗，为期12周。获取收缩动脉压（SAP，毫米汞柱）、左心室/体重比（LV/BW，毫克/克）以及左、右心室胶原容积分数（LVCVF、RVCVF，%），并与年龄/性别匹配的未治疗的RHT大鼠和假手术对照组进行比较。

结果

在RHT中，与对照组相比，SAP显著升高（188±11对125±5毫米汞柱；P<0.001），而在每个治疗组中，SAP均恢复正常。RHT中LV/BW显著增加（2.61±0.12毫克/克；P<0.00001），而在每个治疗组中，LVH完全消退（与未治疗的RHT相比，P<0.002），LV/BW值与对照组相当（1.82±0.03毫克/克），无论使用何种降压药物。在未治疗的RHT中，左心室（LVCVF：12.3±1.9%；与对照组的4.5±0.2%相比，P<0.0005）和右心室（RVCVF：20.6±2.5%；与对照组的8.8±0.4%相比，P<0.00005）均存在心肌纤维化。在用ZOF或NIF治疗的大鼠中，LVCVF分别显著降至5.6±0.4%和5.4±0.6%（与未治疗的RHT相比，P<0.005），RVCVF也有所下降（ZOF：11.0±0.9%；NIF：10.4±2.4%；与未治疗的RHT相比，P<0.007），与对照组无显著差异。相比之下，用LAB治疗未影响心肌纤维化，LVCVF为9.3±1.3%，RVCVF为19.8±2.8%，即与对照组相比仍显著升高（P<0.007）。