Left ventricular insulin-like growth factor I increases in early renal hypertension.

Abstract

Increasing interest has been directed toward the possible role of trophically acting molecules as modulators or initiators, or both, of myocardial hypertrophy. The aim of the present study was to investigate the possible role of one such molecule, namely, insulin-like growth factor I, in myocardial hypertrophy developed in response to renal artery stenosis. Two-kidney, one clip Goldblatt hypertension was induced in Wistar rats weighing 180 g, and sham-operated animals were used as controls. Blood pressure was increased as early as 2 days after clipping (133 ±4 versus 116±4 mm Hg, p<0.05), and the increase persisted 4 and 7 days after clipping (148±6 versus 129±3 mm Hg, p<0.01 and 171±5 versus 139±3 mm Hg,p<0.01, respectively). Left ventricular weight followed a similar pattern (373±7 versus 350±8 mg, NS, 415±11 versus 386±9 ing,/><0.01, and 466±11 versus 391 ±10 mg,/><0.01 at 2, 4, and 7 days after clipping, respectively), but no changes in body weight between the groups were observed. Insulin-like growth factor I messenger RNA (mRNA) was quantified using a solution hybridization assay. W hen challenged by a chronically increased systemic pressure load, the heart responds with an adaptive left ventricular hypertrophy to normalize wall stress and myocardial oxygen consumption (see Friberg 1 ). However, the precise mechanism for transforming the mechanical stimuli of increased pressure or volume work into the hypertrophic response is not known. In addition to mechanical stimuli, different trophic factors such as catecholamines and angjotensin II may influence the From the Departments of Physiology (H.W., J.I., P.F.) and Histology

Increased expression of growth hormone receptor mRNA and insulin-like growth factor-I mRNA in volume-overloaded hearts.

“…27 Moreover, IGF-I has been suggested to be directly involved in cardiac hypertrophy by increasing cardiomyocyte cell size in vitro and by increasing gene expression of myosin light chain-2 and troponin I. 28 In the present study as well as in our previous study on renal hypertensive rats, 7 the left and right ventricles were exposed to identical plasma concentrations of GH, which would imply that the increased myocardial IGF-I expression in response to wall stress was independent of changes in circulating GH levels. Therefore, the finding that RV GH receptor mRNA increased before the expression of IGF-I mRNA is particularly intriguing.…”

“…7 This was further supported by the finding that IGF-I was more abundant in the subendocardial layers of the left ventricle, where wall stress is highest. Activation of the IGF-I gene appeared to be specific because LV levels of y3-actin mRNA were unchanged in hypertensive rats compared with sham- operated rats.…”

“…Activation of the IGF-I gene appeared to be specific because LV levels of y3-actin mRNA were unchanged in hypertensive rats compared with sham- operated rats. 7 To further study the possible influence of wall stress on the expression of IGF-I we modified a model in which volume overload was induced by means of an ACF. In contrast to renal hypertension, in which only the left ventricle is exposed to the increased pressure load, the ACF model allows both ventricles to be subjected to the increased venous return.…”

“…4 - 5 The presence of insulin-like growth factor-I (IGF-I) mRNA in the rat heart has been shown, 6 and it was recently demonstrated that IGF-I mRNA and protein were induced specifically in the pressure-overloaded left ventricle of two-kidney, one clip rats. 7 Presumably, IGF-I gene expression was coupled to the increased left ventricular (LV) workload, and IGF-I thus constitutes a possible mediator of cardiac hypertrophy in response to hemodynamic load. This adds further support to the fact that IGF-I is synthesized in peripheral tissues and exerts paracrine-autocrine effects during tissue growth 8 and that it can be produced in specific regions within the heart.…”

The role of the GH-IGF-I axis in the regulation of myocardial growth: from experimental models to human evidence

“…In models of pressure overload secondary to aortic banding or renal hypertension (17,18), it was shown that IGF-I mRNA expression increased in the myocardium, at an early stage of LV hypertrophy and to a greater extent in the myocardial segments exposed to the highest stress (18,19). Moreover, GHR and IGF-I levels were shown to increase in the right ventricle after induction of volume overload from aorto-caval fistula (19).…”