Interaction between the renin-angiotensin system and insulin-like growth factor I in aorto-caval fistula-induced cardiac hypertrophy in rats

The effects of angiotensin converting enzyme inhibition and angiotensin II receptor blockade on the development of cardiac hypertrophy and myocardial insulin-like growth factor I (IGF-I) in volume overload were studied in mal e Wister rats with aorto-caval fistulas (ACF). Rats were treated with ramip ril (RAM, 3 mg kg(-1) day(-1)) for 4-20 days or losartan (LOS, 10 mg kg(-1) day(-1)) for 2-7 days. Myocardial IGF-I and IGF-I receptor (IGF-I-R) mRNA were determined by solution hybridization. ACF caused hypertrophy of left ( LV) and right ventricles (RV). Hypertrophy appeared on day 2 and reached ma ximal values of +60% in LV and +75% in RV at day 12. Systolic blood pressur e was initially reduced 15% but recovered by day 12. RAM abolished the reco very of blood pressure. Furthermore, RAM attenuated RV hypertrophy by 17% o n day 7 and on day 20, RV weights were close to values found in controls. B eginning on day 9, RAM reduced LV weight back to control levels in parallel to blood pressure. In contrast, LOS affected neither RV nor LV hypertrophy . RV IGF-I mRNA increased 60-100% on day 7 alone in RV in ACF. RAM potentia ted the increase in RV IGF-I to +400% and induced an increase in RV IGF-I-R mRNA on day 7 (+90%) in ACF. LOS did not: affect RV IGF-I. Development of cardiac hypertrophy in ACF seemed independent of angiotensin II. RV hypertr ophy was associated with activation of IGF-I independent of the renin-angio tensin system. IGF-I was further potentiated when development of hypertroph y was attenuated, possibly indicative of a greater urge for compensational growth in a relatively thinner and more volume-distended chamber.