Influence of age on contractile response to insulin-like growth factor 1 in ventricular myocytes from spontaneously hypertensive rats

Citation
J. Ren et al., Influence of age on contractile response to insulin-like growth factor 1 in ventricular myocytes from spontaneously hypertensive rats, HYPERTENSIO, 34(6), 1999, pp. 1215-1222
Citations number
43
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
HYPERTENSION
ISSN journal
0194-911X → ACNP
Volume
34
Issue
6
Year of publication
1999
Pages
1215 - 1222
Database
ISI
SICI code
0194-911X(199912)34:6<1215:IOAOCR>2.0.ZU;2-#
Abstract
Evidence suggests a pathophysiological role of insulin-like growth factor 1 (IGF-1) in hypertension. Cardiac function is altered with advanced age, si milar to hypertension. Accordingly, the effects of IGF-1 on cardiac myocyte shortening and intracellular Ca2+ were evaluated in hypertension at differ ent ages. Ventricular myocytes were isolated from Wistar-Kyoto rats (WKY) a nd spontaneously hypertensive rats (SHR), aged 12 and 36 weeks. Mechanical and intracellular Ca2+ properties were examined by edge-detection and fluor escence microscopy. At 12 weeks, IGF-1 (1 to 500 ng/mL) increased peak twit ch amplitude (PTA) and FFI changes (Delta FFI) in a dose-dependent manner i n WKY myocytes, with maximal increases of 27.5% and 35.2%, respectively, Ho wever, IGF-1 failed to exert any action on PTA and Delta FFI in the age-mat ched SHR myocytes. Interestingly, at 36 weeks, IGF-1 failed to exert any re sponse in WKY myocytes but depressed both PTA and Delta FFI in a dose-depen dent manner in SHR myocytes, with maximal inhibitions of 40.5% and 16.1%, r espectively. Myocytes from SHR or 36-week WKY were less sensitive to norepi nephrine (1 mu mol/L) and KCl (30 mmol/L). Pretreatment with nitric oxide s ynthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 100 mu mol /L) did not alter the IGF-1-induced response in 12-week WKY myocytes but un masked a positive action in 12-week SHR and 36-week WKY myocytes. L-NAME al so significantly attenuated IGF-1-induced depression in 36-week SHR myocyte s. In addition, the Ca2+ channel opener Bay K8644 (1 mu mol/L) abolished IG F-l-induced cardiac depression in 36-week SHR myocytes. Collectively, these results suggest that the IGF-l-induced cardiac contractile response was re duced with advanced age as well as with hypertension. Alterations in nitric oxide and intracellular Ca2+ modulation may underlie, in part, the resista nce to IGF-1 in hypertension and advanced age.