With increasing age, cardiac beta-
adrenoceptor function decreases. To study possible mechanisms underlying this process, we assessed in right atrial appendages from 52 patients of different ages (group A, < 20 years, mean age 3.7 +/- 1.0 years, n = 20; group B, 20-50 years, mean age, 37.9 +/- 2.3 years, n = 9; group C, > 50 years, mean age 66.1 +/- 1.5 years, n = 23) without apparent
heart failure who were undergoing open heart surgery beta-
adrenoceptor number and subtype distribution (by (-)-[125I]-
iodocyanopindolol [
ICYP] binding),
adenylyl cyclase activity, and Gs- and Gi-
protein alpha-subunits (by quantitative Western blotting). beta-
Adrenoceptor number in the three groups was not significantly different; in contrast, basal, 10 microM
GTP-, 100 microM
isoprenaline (ISO), 10 mM NaF-, 100 microM
forskolin-, and 10 mM Mn(2+)-stimulated
adenylyl cyclase activity was significantly higher in group A than in group B and was further decreased in group C. Similarly, 100 microM
terbutaline-, 100 microM
histamine-, and 100 microM 5-HT-stimulated
adenylyl cyclase activity significantly decreased from group A to group C. Moreover, all these
adenylyl cyclase parameters were significantly negatively correlated with the age of the patients. Although Gs alpha was not altered, Gi alpha in group C was significantly higher than in group A; moreover, there was a weak but significant positive correlation between Gi alpha and the age of the patients. We conclude that an impairment of the activity of the catalytic unit of
adenylyl cyclase is involved in the decrease in cardiac beta-
adrenoceptor function with age; an increase in Gi alpha might contribute further to the reduced beta-
adrenoceptor function.