Exogenously administered growth hormone and insulin-like growth factor-I alter intracellular Ca2+ handling and enhance cardiac performance : In vitro evaluation in the isolated isovolumic buffer-perfused rat heart

• Published in: Circulation research 1996-08, Vol.79 (2), p.227-236
• Main Authors: STRÖMER, H, CITTADINI, A, DOUGLAS, P. S, MORGAN, J. P
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Buffers; Calcium - metabolism; Calcium - pharmacology; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Growth Hormone - pharmacology; Heart; In Vitro Techniques; Insulin-Like Growth Factor I - pharmacology; Intracellular Membranes - metabolism; Myocardium - cytology; Myocardium - metabolism; Perfusion; Rats; Rats, Sprague-Dawley; Ventricular Function, Left - drug effects; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.79.2.227

It has been proposed that chronic treatment with growth hormone (GH) or insulin-like growth factor-I (IGF-I) in the rat may enhance cardiac function in vivo. To confirm these findings and elucidate the mechanisms by which cardiac function is modulated, we studied isolated buffer-perfused rat hearts after 4 weeks of treatment with high doses of GH and IGF-I alone or in combination. Mechanical parameters were measured at 50% of the intracardiac balloon volume at which maximal developed pressure (DevP) occurred. EC50 of the force-Ca2+ relationship and maximal Ca(2+)-activated systolic wall stress (max sigma s) were assessed by increasing Ca2+ in the perfusate in a stepwise fashion and plotting systolic wall stress (sigma s) versus intracellular peak systolic Ca2+, measured by the aequorin bioluminescence method. We found a marked increase of systolic pressure (Ps), DevP, and (+dP/dt)/DevP in the treated groups compared with the control group. The combination group showed a blunted effect. sigma s was increased in all treated groups for a perfusate Ca2+ concentration of > 1.5 mmol/L. The enhanced systolic performance can be explained by an increase of the overall Ca2+ responsiveness due to an increased maximal response to Ca2+ even though the EC50 of the Ca(2+)-dose response was also slightly increased. Ps was further enhanced by an increase of the relative wall thickness induced by the treatment. Diastolic pressure, diastolic Ca2+, and the amplitude and time course of the Ca2+ transient were not influenced by any treatment protocol. All treatments caused increases of body and heart weight. These data support the hypothesis that both IGF-I and GH directly affect cardiac performance by altering cardiac geometry as well as by enhancing max sigma s.