Alterations in responsiveness to stimulation of G protein-coupled receptors in the cardiovascular system have been noted during aging and may be due to changes in the G proteins. The levels of G protein alpha subunits (Gs alpha, G(o) alpha and Gi alpha) and their mRNAs (Gs alpha, G(o) alpha, Gi2 alpha and Gi3 alpha) were examined in the aorta, heart, and brain of 6 and 24 month old fischer 344 rats by Western blot analysis, quantitative RNA dot blot hybridization and Northern Blot analysis. There were four bands (52, 45, 42 and 38 kD) in the aorta for Gs alpha. The 42 kD band decreased significantly in 24 month old rats (69.2 +/- 0.2%, P < 0.05), while the other bands did not change. The Go alpha and the Gi alpha contain respectively only a band of 39 kD and of 41 kD which decreased significantly in the 24 month rats by 71.8 +/- 10.7% and 63.1 +/- 10.4%; There were no significant changes in the level of G alpha mRNA between 6 and 24 month old rats. In the heart anti-Gs alpha antiserum could detect 3 bands (52, 45 and 42 kD) which did not change during aging; the levels of Gi alpha and G(o) alpha also did not change, but the mRNAs for Gi2 alpha and Gi3 alpha were significantly increased respectively to 120.8 +/- 8.4% and 136.4 +/- 14.2%. The above results indicated that the decrease of levels of Gi alpha G(o) alpha expression may be the molecular basis for the alterations in signal transduction and biological response of aging aorta and heart.