Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle.

Abstract

We studied papillary muscle mechanics and energetics, myosin phenotype, and ATPase activities in left ventricles from rats bearing a growth hormone (GH)-secreting tumor. 18 wk after tumor induction, animals exhibited a dramatic increase in body weight (+101% vs. controls) but no change in the ventricular weight/body weight ratio. The maximum isometric force of papillary muscles normalized per cross-sectional area rose markedly (+42%, P < 0.05 vs. controls), whereas the maximum unloaded shortening velocity did not change. This was observed despite a marked isomyosin shift towards V3 (32±5% vs. 8±2% in controls, P < 0.001). Increased curvature of the force-velocity relationship (+64%, P < 0.05 vs. controls) indicated that the muscles contracted more economically, suggesting the involvement of V3 myosin. Total calcium-and actinactivated myosin ATPase activities assayed on quickly frozen left ventricular sections were similar in tumor-bearing rats and in controls. After alkaline preincubation, these activities only decreased in tumor-bearing rats, demonstrating that V3 enzymatic sites were involved in total ATPase activity. These data demonstrate that chronic GH hypersecretion in the rat leads to a unique pattern of myocardial adaptation which allows the muscle to improve its contractile performance and economy simultaneously, thanks to myosin phenoconversion and an increase in the number of active enzymatic sites. (J. Clin. Invest.

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

“…Signals for myocardial growth include metabolic factors such as GH/IGF-I hypersecretion (10,11) and insulin resistance (39), and haemodynamic factors such as pressure and volume overload (40). The clinical importance of these factors has been documented largely in patients with essential hypertension, obesity, abnormalities of glucose tolerance and diabetes mellitus, in whom LVH and diastolic dysfunction have been linked to insulin resistance (41 -43).…”

“…From a physiopathological point of view, it is well accepted that growth hormone/insulin-like growth factor-I (GH/IGF-I) hypersecretion in itself contributes to the existence of a specific cardiomyopathy (6,9), the myocardial effects of chronic GH excess and the direct growth-promoting role of IGF-I being supported by in vivo (10) and in vitro experimental models (11) respectively. Other factors, however, could contribute to the increased cardiovascular risk reported in patients with acromegaly.…”

Myocardial hypertrophy in transgenic mice overexpressing the bovine growth hormone (bGH) gene

“…The effects of GH are frequently mediated by endocrine-or para/autocrine-produced insulin-like growth factor-1 (IGF-1), and indeed IGF-1-specific mRNA is upregulated in the hypertrophic myocardium [22]. It has also been demonstrated that an excess of GH improves the contractility of the myocardium by prolonging the action potential and increasing the calcium influx [23,24] and, furthermore, inducing phenoconversion [23]. However, one of the possible regulators in the process of cardiac muscle hypertrophy, the interplay between the sympathetic and the parasympathetic nervous system, has not been studied.…”

Recombinant Human Growth Hormone Treatment for Dilated Cardiomyopathy in Children

“…GH/IGF-1 signaling augments the force-generating machinery of myocytes by down-regulating cytoskeletal proteins, thus facilitating myofibril assembly and growth, and up-regulating certain contractile proteins. 13,28 Expansion of the contractile apparatus causes myocyte hypertrophy, which leads to increased wall thickness and consequent attenuation of LV wall stress (assuming that wall thickness increases more than the chamber radius) and thus myocardial oxygen consumption. Indeed, we observed decreased wall stress and fiber stress in response to GH treatment.…”

“…[7][8][9][10][11][12] GH/IGF-1 signaling also stimulates myosin phenoconversion, with a shift toward more energy-efficient isoforms, as well as sympathetic deactivation, inhibition of inflammatory cytokine generation and apoptosis, and attenuation of the local and systemic renin-angiotensin systems. 7,[13][14][15][16] Fazio et al 17 suggested that GH therapy may improve cardiac function among adults with DCM, although data from other human studies are equivocal. [18][19][20][21][22] On the basis of the importance of the GH/IGF-1 axis in the maintenance of normal myocardial function and data from experimental models and adults with heart failure, we hypothesized that GH might provide a pharmacologic means of improving LV energetics and normalizing the neurohormonal milieu, thus optimizing cardiac function, among children with DCM.…”