Left ventricular  1 and  2 adrenoceptor mRNA expression in normal and volume overloaded human heart

Study objective - The aim was to determine gene expressions of beta-1 and beta-2 adrenoceptor subtypes (BAR-1, BAR-2) in normal and volume overloaded human heart. Design - Tissue mRNA levels were determined by excess solution hybridisation using S-35-UTP labelled BAR-1 and BAR-2 cRNA probes. Material - Atrium, right and left ventricular subendocardium, and papillary muscle from donor hearts and papillary muscle from patients operated for mitral stenosis and mitral regurgitation were studied. Measurements and main results - The basal levels of myocardial BAR-1 and BAR-2 mRNA expression were similar to the levels in human adipose tissue that have been reported previously from our laboratory (10-15 amol mRNA-mu-g-1 total nucleic acids). No differences in BAR-1 and BAR-2 mRNA expression were observed between various parts of the normal heart. In papillary muscle, BAR-1 and BAR-2 mRNA levels were 8.8 (SEM 5.1) and 10.2(6.6) amol-mu-g-1 total nucleic acids, respectively. Furthermore, no differences in BAR mRNA expression were observed between myocardium subjected to mitral stenosis as compared to normal myocardium. On the other hand, patients with mitral regurgitation expressed significantly lower levels of both BAR-1 and BAR-2 mRNA, at 4.8(1.0) (p < 0.05) and 2.6(1.1) (p < 0.001) amol-mu-g-1 total nucleic acids, respectively. The ratio BAR-1/BAR-2 mRNA was higher (p < 0.01) in mitral regurgitation than in the normal heart. Conclusions - Myocardium from different parts of the normal human heart, where different pressure work is generated, express similar levels of BAR-1 and BAR-2 mRNA. With volume load a significant decrease in BAR mRNA levels was observed, which was more marked for BAR-2 mRNA. This difference in specific mRNA levels in patients with mitral regurgitation indicates an independent regulation of the expression of these two receptor subtypes.