Decreased accumulation of beta 1-adrenergic receptor, G alpha s and total myosin heavy chain messenger RNAs in the left ventricle of senescent rat heart.

The expression of genes coding for the beta 1-adrenergic receptor (beta 1-AR), the alpha subunit of Gs and total myosin heavy chain (MHC) was compared between left ventricles (LV's) from young (6-7 weeks old) and old (22 months old) rats. The mRNA levels were quantitated by Northern or Slot blots analyses using specific DNA probes. Ageing was found to be associated with a reduction in beta 1-AR (77%), G alpha s (33%) and, total MHC (51%) mRNA levels with no concomitant change in 18S RNA and poly(A+) mRNA levels. These results indicate that transcriptional and/or post-transcriptional mechanisms participate in the control of beta-adrenergic receptor density during ageing. As in the senescent LV, beta 1-AR mRNA level is reduced in the hypertrophied LV, whereas the level of G alpha s mRNA is reduced in the senescent but not in the hypertrophied LV. From our data we conclude (1) that a dual mechanism may operate during ageing, mechanical factors indirectly regulating beta 1-AR mRNA level, while changes in G alpha s mRNA level do not depend on hemodynamic load and (2) that the re-expression of beta-MHC mRNA does not compensate for the decreased accumulation of alpha-MHC mRNA which results in a large decrease in the level of total MHC mRNA in the senescent LV.