lithium-chloride and Hypertrophy--Left-Ventricular

Myocardial hypertrophy has been recognized to be an adaptive response to a variety of external stimuli (e.g., myocardial infarction, pressure overload, catecholamine treatment, endocrine disorders) that are involved in several subcellular factors that mediate signaling pathways, from external stimuli to nuclear protein synthesis. Glycogen synthase kinase-3beta (GSK-3beta) is one of the subcellular factors that regulate nuclear transcription factors, such as activated T-cell (NFAT) proteins, that are related to gene programming during cardiac hypertrophy. On the other hand, GSK-3beta, known as a regulator of cardiomyocyte growth in Wnt signaling of cardiogenesis, is involved in beta-catenin degradation. Inhibition of GSK-3beta has been reported to induce cardiac hypertrophy. Tateishi et al. demonstrated in an aortic constriction-induced acute hypertrophy model using 6-week-old Wister rats that if GSK-3b is inhibited by LiCl up-regulated beta-catenin expression and additional hypertrophy were observed. They suggested that Li(2+) had an additive effect on pressure overload-induced hypertrophy through the GSK-3beta-beta-catenin pathway. Their article provides promising information on the mechanism of hypertrophic myocyte growth during acute pressure overload.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; beta Catenin; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypertension; Hypertrophy, Left Ventricular; Ligation; Lithium Chloride; Phosphorylation; Protein Kinase Inhibitors; Rats; RNA, Messenger; Serine; Time Factors

A large number of diverse signaling molecules in cell and animal models participate in the stimulus-response pathway through which the hypertrophic growth of the myocardium is controlled. However, the mechanisms of signaling pathway including the influence of lithium, which is known as an inhibitor of glycogen synthase kinase-3beta, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3beta inhibition by lithium has acute effects on the myocyte growth mechanism in a pressure overload rat model.. First, we created a rat model of acute pressure overload cardiac hypertrophy by abdominal aortic banding. Protein expression time courses for beta-catenin, glycogen synthase kinase-3beta, and phosphoserine9-glycogen synthase kinase-3beta were then examined. The rats were divided into four groups: normal rats with or without lithium administration and pressure-overloaded rats with or without lithium administration. Two days after surgery, Western blot analysis of beta-catenin, echo-cardiographic evaluation, left ventricular (LV) weight, and LV atrial natriuretic peptide mRNA levels were evaluated.. We observed an increase in the level of glycogen synthase kinase-3beta phosphorylation on Ser 9. A significant enhancement of LV heart weight (P < 0.05) and interventricular septum and posterior wall thickness (P < 0.05) with pressure-overloaded hypertrophy in animals treated with lithium were also observed. Atrial natriuretic peptide mRNA levels were significantly increased with pressure overload hypertrophy in animals treated with lithium.. We have shown in an animal model that inhibition of glycogen synthase kinase-3beta by lithium has an additive effect on pressure overload cardiac hypertrophy.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; beta Catenin; Blood Pressure; Blotting, Western; Cardiovascular Agents; Disease Models, Animal; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypertension; Hypertrophy, Left Ventricular; Ligation; Lithium Chloride; Male; Phosphorylation; Polymerase Chain Reaction; Protein Kinase Inhibitors; Rats; Rats, Wistar; RNA, Messenger; Serine; Time Factors; Ultrasonography