Tatsuyuki Onodera

Estimation of cardiac hypertrophy in goldblatt hypertensive rats by using echocardiography

The purpose of this study was to examine activator protein-1 (AP1) and nuclear factor-KB (NF-KB) DNA binding activity, which seem to be important in a signal transduction cascade upstream of the increased level of mRNA expression observed in isoproterenol-induced left ventricular hypertrophy. Rats were continuously infused with saline and low or high dose of isoproterenol (0.5 or 3 mg/kg/day) by an osmotic minipump for 12 hr, 24 hr, 48 hr or 72 hr.AP-1 and NF-KB DNA binding activity was determined using an electrophoretic mobility shift assay. Levels of ANP and c~-skeletal actin mRNAs were analyzed by Northern bJot hybridization. AP-1 DNA binding activities by low or high dose of [soproterenol administration were increased at 12 hr, reached their peak 24.1and 37.1-fold (P<0.01) at 24 hr, and thereafter declined. Although N F-KB DNA binding activities by low dose of isoprotenol did not change, it by high dose increased to 6.0-fold (P<0.01) at 48 hr. Moreover, levels of ANP and c~skeletal actin mRNAs increased 8.0and 3.5-fold (P<0.01) by low dose, and 14.3and 6.2-fold (P<0.01) by high dose at 48 hr. Isoproterenol by high dose induced severe hypertrophy of myocyte and necrosis by histological examination. NF-KB DNA binding activities may be induced by an inflammatory response following myocardial injury. On the other hand, AP-1 DNA binding activity peaked at day1 in both low dose and high dose and levels of ANP and c~-skeltal actin mRNAs peaked at day 2. AP-1 DNA binding activity intially increased followed by increased expression of ANP and c~-skeletal actin mRNAs and these signal transduction mechasism may contribute to the isoproterenolinduced hypertrophy.