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(Hypertension. 1999;34:1215.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Influence of Age on Contractile Response to Insulin-Like Growth Factor 1 in Ventricular Myocytes From Spontaneously Hypertensive Rats

Jun Ren; LeQuishia Jefferson; James R. Sowers; Ricardo A. Brown

From the Department of Physiology (J.R.), University of North Dakota, Grand Forks, and the Departments of Physiology (L.J., R.A.B.) and Internal Medicine (J.R.S.), Wayne State University School of Medicine, Detroit, Mich.

Correspondence to Ricardo A. Brown, PhD, Department of Physiology, Wayne State University School of Medicine, 540 E Canfield Ave, Detroit, MI 48201. E-mail rbrown{at}med.wayne.edu

Abstract—Evidence suggests a pathophysiological role of insulin-like growth factor 1 (IGF-1) in hypertension. Cardiac function is altered with advanced age, similar to hypertension. Accordingly, the effects of IGF-1 on cardiac myocyte shortening and intracellular Ca²⁺ were evaluated in hypertension at different ages. Ventricular myocytes were isolated from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), aged 12 and 36 weeks. Mechanical and intracellular Ca²⁺ properties were examined by edge-detection and fluorescence microscopy. At 12 weeks, IGF-1 (1 to 500 ng/mL) increased peak twitch amplitude (PTA) and FFI changes (FFI) in a dose-dependent manner in WKY myocytes, with maximal increases of 27.5% and 35.2%, respectively. However, IGF-1 failed to exert any action on PTA and FFI in the age-matched SHR myocytes. Interestingly, at 36 weeks, IGF-1 failed to exert any response in WKY myocytes but depressed both PTA and FFI in a dose-dependent manner in SHR myocytes, with maximal inhibitions of 40.5% and 16.1%, respectively. Myocytes from SHR or 36-week WKY were less sensitive to norepinephrine (1 µmol/L) and KCl (30 mmol/L). Pretreatment with nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 100 µmol/L) did not alter the IGF-1–induced response in 12-week WKY myocytes but unmasked a positive action in 12-week SHR and 36-week WKY myocytes. L-NAME also significantly attenuated IGF-1–induced depression in 36-week SHR myocytes. In addition, the Ca²⁺ channel opener Bay K8644 (1 µmol/L) abolished IGF-1–induced cardiac depression in 36-week SHR myocytes. Collectively, these results suggest that the IGF-1–induced cardiac contractile response was reduced with advanced age as well as with hypertension. Alterations in nitric oxide and intracellular Ca²⁺ modulation may underlie, in part, the resistance to IGF-1 in hypertension and advanced age.

Key Words: insulin growth factor • hypertension, essential • aging • myocytes • calcium

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