Intrinsic cardiac muscle function, calcium handling and beta -adrenergic responsiveness is impaired in rats with growth hormone deficiency.
To evaluate whether growth hormone (GH) is required for normal cardiac muscle function, we studied left ventricular papillary muscles of mutant GH-deficient rats. Developed tension normalized by cross-sectional area (DT), intracellular [Ca(2+)](i)(aequorin method) and beta-adrenergic responsiveness were assessed with or without 3 weeks GH replacement therapy and compared to normal controls. Steady-state force-Ca(2+)relationship was determined in tetanized ryanodine-treated muscles. beta-adrenergic responsiveness was tested during graded isoproterenol stimulation. [Ca(2+)](i)at baseline and the EC(50)of the force-Ca(2+)relationship were similar in all groups. In dwarf rats, DT at baseline was reduced by 43% compared to controls, due to a decreased maximal Ca(2+)-activated force. beta-adrenergic responsiveness of systolic Ca(2+)-release and mechanical function were depressed in dwarf rats. GH treatment caused at least partial improvement of the depressed parameters. These data support the hypothesis that GH is required for normal intrinsic function of cardiac muscle by maintaining Ca(2+)- and beta-adrenergic responsiveness.
Strömer
H
H
Medizinische Universitätsklinik, Würzburg, Germany. stromer@mail.uni-wuerzburg.de
Cittadini
A
A
Grossman
J D
JD
Douglas
P S
PS
Morgan
J P
JP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013006:Growth Hormone / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains; D013718:Tensile Strength
D000318:Adrenergic beta-Agonists; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D007545:Isoproterenol; D002118:Calcium