Donohue T J, Dworkin L D, Ma J, Lango M N, Catanese V M
Division of Molecular Endocrinology, New York University School of Medicine, New York 10016, USA.
J Investig Med. 1997 Dec;45(9):584-91.
Left ventricular hypertrophy (LVH) is a generalized adaptation to altered myocardial load. Hypertension induces significant increases in ventricular IGF-I gene expression that occur coordinately with development of LVH. To test whether IGF-I promotes initiation of LVH, we examined ventricular IGF-I mRNA content in spontaneously hypertensive rats (SHRs) treated with antihypertensive drugs that limit or permit LVH.
Prehypertensive SHRs were left untreated or treated with enalapril, nifedipine, or hydralazine. Systolic blood pressure (SBP), hypertrophy index (ventricular weight/body weight), and ventricular IGF-I mRNA levels were examined 2, 4, and 6 weeks after beginning therapy in the experimental groups.
Systolic blood pressure reached hypertensive levels after 2 weeks in untreated animals, and was controlled in the treated animals. The hypertrophy index in untreated animals was significantly elevated at 4 weeks. By 6 weeks, the hypertrophy indices of both the enalapril- and nifedipine-treated groups were significantly lower than that of the untreated group. In contrast, the hypertrophy index of the hydralazine-treated animals remained comparable to that of the untreated animals. By 4 weeks, IGF-I mRNA levels in the enalapril- and nifedipine-treated groups were significantly lower than those in the untreated and hydralazine-treated groups.
We conclude that: (1) antihypertensive drugs that reduce LVH blunt ventricular IGF-I mRNA content; and (2) the hemodynamic effects of antihypertensives may be dissociated from their ability to promote or limit a hypertrophic response. The clear association of LVH with ventricular IGF-I mRNA content suggests that IGF-I is an important determinant of ventricular growth. Our data also suggest that angiotensin-converting enzyme inhibitors and calcium channel blockers may reduce LVH by inhibiting cardiac IGF-I gene expression.
左心室肥厚（LVH）是对心肌负荷改变的一种全身性适应。高血压会导致心室IGF-I基因表达显著增加，且这种增加与LVH的发展协同发生。为了检验IGF-I是否促进LVH的起始，我们检测了用限制或允许LVH发展的抗高血压药物治疗的自发性高血压大鼠（SHRs）心室中IGF-I mRNA的含量。
将高血压前期的SHRs不做处理或用依那普利、硝苯地平或肼屈嗪进行治疗。在实验组开始治疗2、4和6周后检测收缩压（SBP）、肥厚指数（心室重量/体重）和心室IGF-I mRNA水平。
未治疗的动物在2周后收缩压达到高血压水平，而治疗组的血压得到控制。未治疗动物的肥厚指数在4周时显著升高。到6周时，依那普利和硝苯地平治疗组的肥厚指数均显著低于未治疗组。相比之下，肼屈嗪治疗动物的肥厚指数仍与未治疗动物相当。到4周时，依那普利和硝苯地平治疗组的IGF-I mRNA水平显著低于未治疗组和肼屈嗪治疗组。
我们得出以下结论：（1）降低LVH的抗高血压药物可降低心室IGF-I mRNA含量；（2）抗高血压药物的血流动力学效应可能与其促进或限制肥厚反应的能力无关。LVH与心室IGF-I mRNA含量的明确关联表明IGF-I是心室生长的重要决定因素。我们的数据还表明，血管紧张素转换酶抑制剂和钙通道阻滞剂可能通过抑制心脏IGF-I基因表达来减轻LVH。
