Study of cardiac hypertrophy--humoral factors that stimulate protein metabolism of cultured rat heart cells

Abstract

Recent extensive studies suggested that some humoral factors may contribute to the development and/or reversal of cardiac hypertrophy in hypertension. The purpose of this study is to examine whether there exists humoral factor(s) for cardiac hypertrophy in experimental perinephritic hypertension in dogs. Hypertension was induced by the method of Page with some modifications. Humoral factors were studied using a microassay system that was independent of pressure overload, hemodynamic effects, and other factors. L(-)-isoproterenol (ISO) and angiotensin II (AngII) increased the uptake of 3H-uridine into 10-day-old cultured heart cells. The maximal response to ISO or AngII was obtained by 10(-5) M ISO or 10(-10) M AngII, and the percent increments in the uptake of 3H-uridine was 38.4 +/- 20.4%, and 45.1 +/- 22.5%, respectively. Moreover, ISO, DL-noradrenaline, and AngII stimulated protein synthesis of 7-day-old or 14-day-old cultured heart cells in this order (9.5 +/- 1.5, 7.3 +/- 1.2, 2.0 +/- 0.5 micrograms/6 x 10(5) by 7-day-old heart cells; 23.8 +/- 8.3, 19.0 +/- 9.4, 4.4 +/- 1.1 micrograms/6 x 10(5) by 14-day-old heart cells). Heart and kidney extracts were obtained from experimental perinephritic hypertensive dogs and sham-operated dogs. The heart extract obtained from hypertrophied left ventricle (LV) of the experimental hypertensive dogs, but not of the sham-operated dogs, increased the uptake of 3H-uridine into 10-day-old heart cells. The mean percent increment in uptake of 3H-uridine induced by the hypertrophied LV heart extract at a final concentration of 5 x 10(-3)% V/V (1-3 micrograms) in different experiments was about 15%. High performance liquid chromatography (HPLC) demonstrated that the LV heart extract obtained from the perinephritic hypertensive dogs contained at least 16 molecules. Among them, one with a molecular weight of approximately 11,200 daltons stimulated uptake of both 3H-uridine and 14C-leucine into cultured heart cells. These results demonstrated that heart extract obtained from hypertrophied LV of perinephritic hypertensive dogs contained at least one factor which may induce and/or modulate myocardial hypertrophy in this model for hypertension.