Angiotensin II receptor gene expression in hypertrophied left ventricles of rat hearts

OBJECTIVETo examine the expression of angiotensin II AT1a, AT1b and AT2 receptor genes in the left ventricles of rats subjected to ventricular pressure overloading induced by aortic banding for 6 weeks and then 6 weeks medical treatment RESULTSAortic banding was related to an increase in relative weight of the left ventricle from 1.73 ±0.06 (shamoperated) to 2.81 ± 0.25 g/kg, an increase in p-myosin:amyosin messenger RNA (mRNA) ratio from 0.30 ±0.02 to 1.94 ±0.55 and an 18-fold increase in left ventricular atrial natriuretic peptide mRNA levels. In contrast, left ventricular pressure overload hypertrophy was not related to a significant change in the abundance of AT1a and AT1b mRNA, which were expressed in a relative ratio of 51. Similarly, the abundance of AT2 mRNA was not significantly changed in hypertrophied ventricles. In rats receiving the angiotensin II AT1 receptor antagonist losartan (40mg/kg) for 6 weeks after banding, relative heart weights were 2.39 ± 0.14 g/kg, the p-myosinα-myosin ratio was 1.04 ±0.20 and atrial natriuretic peptide mRNA levels displayed a blunted increase (11-fold over sham-treated controls), documenting a significant amelioration of left ventricular hypertrophy by blockade of the AT1 receptor. CONCLUSIONLosartan treatment in parallel did not affect AT1a, AT1b and AT2 receptor mRNA levels, which were not different from those in vehicle-treated or sham-treatedcontrols. These findings confirm that left ventricular hypertrophy in the rat is associated with increased ventricular expression of β-myosin and of atrial natriuretic peptide and with reduced expression of α α-myosin. Despite these significant changes in cardiac gene expression no alteration was observed in AT1a, AT1b and AT2 receptor mRNA levels.