Consequences of growth hormone deficiency on cardiac structure, function, and beta-adrenergic pathway: studies in mutant dwarf rats.
To evaluate GH's role in cardiac physiology and its interrelationship with the beta-adrenergic system, we studied GH-deficient dwarf (dw/dw) and control rats in 4 groups of 20 each: dwarf group receiving placebo, dwarf-GH group receiving 2 mg/kg GH, dwarf-GH-propranolol group receiving 2 mg/kg GH and 750 mg/liter propranolol, and a control group of Lewis rats receiving placebo. Dwarf rats showed reduced left ventricular weight and myocyte cross-sectional area, and impaired cardiac performance in vitro. Left ventricular pressure-volume curves showed a shift upward and leftward, indicating reduced distensibility. These abnormalities reversed after GH treatment regardless of concomitant propranolol administration. Although isoproterenol responsiveness was reduced in dwarf rats, there were no differences in beta-adrenergic receptor density, affinity, Na+,K+-adenosine triphosphatase activity, or adenylyl cyclase activity. In summary, myocyte size, cardiac structure, myocardial contractility, and distensibility are abnormal in GH deficiency. The effects of GH are not mediated by the beta-adrenergic pathway, which, in turn, is unaffected by changes in the GH-insulin-like growth factor I axis. Thus, GH plays a regulatory role in normal cardiac physiology that is independent of the beta-adrenergic system.
Cittadini
A
A
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Strömer
H
H
Vatner
D E
DE
Grossman
J D
JD
Katz
S E
SE
Clark
R
R
Morgan
J P
JP
Douglas
P S
PS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004392:Dwarfism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D013006:Growth Hormone; D011433:Propranolol; D007545:Isoproterenol