ANTIHYPERTENSIVE AGENTS THAT LIMIT VENTRICULAR HYPERTROPHY INHIBIT CARDIAC EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I

Background: Left ventricular hypertrophy (LVH) is a generalized adapta tion to altered myocardial load, Hypertension induces significant incr eases in ventricular IGF-I gene expression that occur coordinately wit h development of LVH. To test whether IGF-I promotes initiation of LVH , we examined ventricular IGF-I mRNA content in spontaneously hyperten sive rats (SHRs) treated with antihypertensive drugs that limit or per mit LVH. Methods: Prehypertensive SHRs were left untreated or treated with enalapril, nifedipine, or hydralazine, Systolic blood pressure (S EP), hypertrophy index (ventricular weight/body weight), and ventricul ar IGF-I mRNA levels were examined 2, 4, and 6 weeks after beginning t herapy in the experimental groups. Results: Systolic blood pressure re ached 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, BS 6 weeks, the hypertr ophy indices of both the enalapril- and nifedipine-treated groups were significantly lower than that of the untreated group, In contrast, th e hypertrophy index of the hydralazine-treated animals remained compar able to that of the untreated animals, By 4 weeks, IGF-I mRNA levels i n the enalapril- and nifedipine-treated groups were significantly lon er than those in the untreated and hydralazine-treated groups. Conclus ions: We conclude that: (1) antihypertensive drugs that reduce LVH blu nt 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 ventr icular IGF-I mRNA content suggests that IGF-I is an important determin ant of ventricular growth. Our data also suggest that angiotensin-conv erting enzyme inhibitors and calcium channel blockers may reduce LVH b y inhibiting cardiac IGF-I gene expression.