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

Objective. To examine the expression of angiotensin II AT(1a), AT(1b) 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. Results. Aortic banding was related to an increase in relative weight of the left ventricle from 1.73 ± 0.06 (sham-operated) to 2.81 ± 0.25 g/kg, an increase in β-myosin:α-myosin 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 AT(1a) and AT(1b) mRNA, which were expressed in a relative ratio of 5:1. Similarly, the abundance of AT₂ mRNA was not significantly changed in hypertrophied ventricles. In rats receiving the angiotensin II AT₁ receptor antagonist losartan (40 mg/kg) for 6 weeks after banding, relative heart weights were β-myosin:α-myosin ratio was 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. Conclusion. Losartan treatment in parallel did not affect AT(1A), AT(1b) and AT₂ receptor mRNA levels, which were not different from those in vehicle-treated or sham-treated controls. 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-myosin. Despite these significant changes in cardiac gene expression no alteration was observed in AT(1A), AT(1b) and AT₂ receptor mRNA levels.