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(Hypertension. 1999;34:1053-1059.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Angiotensin II Stimulates Gene Expression of Cardiac Insulin-Like Growth Factor I and Its Receptor Through Effects on Blood Pressure and Food Intake

Marijke Brink; Jacqueline Chrast; S. Russ Price; William E. Mitch; Patrick Delafontaine

From the Division of Cardiology (M.B., J.C., P.D.), University Hospital of Geneva, Switzerland; and the Renal Division (S.R.P., W.E.M.), Emory University Medical School, Atlanta, Ga.

Correspondence to Marijke Brink, PhD, Department of Medicine, Division of Cardiology, University of Geneva, Ave de la Roseraie 64, CH-1211 Geneva, Switzerland. E-mail marijke.brink{at}dim.hcuge.ch

Abstract—Angiotensin II (Ang II) is known to act as a growth factor and may be involved in cardiac remodeling. We have shown that insulin-like growth factor-I (IGF-I) is an autocrine mediator of growth responses to Ang II in vascular smooth muscle cells in vitro, and we hypothesized that IGF-I also serves as an important modulator of cardiovascular growth in vivo. To study the effect of Ang II on cardiac IGF-I, we infused rats for 3, 7, or 14 days with Ang II through osmotic minipumps. After 7 days, left ventricular mass normalized for body weight was increased by 20% (P<0.01) in Ang II rats compared with pair-fed control rats that were given a restricted amount of food identical to that eaten by the anorexic, Ang II–infused rats. Ang II increased left ventricular IGF-I mRNA levels by 1.5- to 1.8-fold compared with ad libitum–fed or pair-fed control rats (P<0.05). Cardiac IGF-I protein was increased correspondingly and was localized on the cardiomyocytes. Treatment with hydralazine abolished the induction of IGF-I mRNA, which indicates that Ang II induces cardiac IGF-I mRNA expression through a pressor-mediated mechanism. IGF-I receptor (IGF-IR) mRNA was induced 2.1-fold in Ang II rats compared with ad libitum–fed rats (P<0.01). However, this increase was also observed in pair-fed controls and is thus due to the anorexigenic effect of Ang II. We have recently shown that circulating IGF-I levels are reduced in response to Ang II infusion. Elevation of IGF-I levels by coinfusion of IGF-I and Ang II significantly increased left ventricular index by 16% compared with rats infused with Ang II alone (P<0.05). In conclusion, autocrine upregulation of cardiac IGF-I and IGF-IR mRNA by Ang II occurs through hemodynamic and nonhemodynamic mechanisms, respectively, and may modulate cardiac structural changes that occur in hypertension.

Key Words: hypertrophy, cardiac • heart failure • growth substances • angiotensin II • immunohistochemistry

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