Age-related changes in G proteins in rat aorta.

Blood vessels from aged animals and humans have impaired relaxation to beta-adrenergic stimulation. We hypothesized that a loss of stimulatory G protein (Gs) or an increase in inhibitory G proteins (Gi) could explain this impairment. Aortic membranes from Fischer 344 rats of 4 age groups (6 week to 24 month) were studied. G-protein levels were initially assessed using cholera and pertussis toxin labeling. There was a marked decline in cholera toxin labeling (which primarily labels Gs alpha) from 6 weeks to 6 months which persisted in 12-month and 24-month animals. Pertussis toxin labeling (which primarily labels Gi alpha) showed only a slight decline with age. Western blotting was performed using specific antibodies for the alpha subunit of Gs, Gi1&2, Gi3, and G beta. There was no significant change in Gs alpha, Gi alpha, or G beta protein levels with age. We conclude there is a loss of cholera toxin-catalyzed ADP ribosylation with age, which does not represent a loss of the stimulatory alpha subunit of G protein. These data suggest that the loss of cholera toxin labeling seen with age may be a marker for loss of Gs alpha function.