AGE-RELATED-CHANGES IN ADENYLYL-CYCLASE ACTIVITY IN RAT AORTA MEMBRANES

Blood vessels from aged animals and humans have impaired relaxation an d cAMP production to beta-adrenergic stimulation. Direct activators of adenylyl cyclase (AC) such as forskolin are not affected. We hypothes ized that analogous findings would occur in membrane preparations. Aor tic media membrane preparations from Fischer 344 rats of four age grou ps (6 weeks to 24 months) were studied. Basal AC activity increased si gnificantly with age. Forskolin-stimulated activity compared to basal tended to be greater in the 6-week and 6-month preparations compared t o the 12- and 24-month preparations. AC activity was assessed in the p resence of the G protein activators (GTP, GppNHp, NaF). There was no a ge-related decrease in responsiveness. The receptor agonists isoproter enol (beta-adrenergic), and PGE-1 (prostaglandin), were studied. There was no significant age-related change in responsiveness over basal ac tivity to either of these agonists. There was a slight, but significan t increase in the isoproterenol responsiveness over GTP responsiveness in the 6-week-old animals which also approached significance in the 6 -month-old animals, but was not seen in the 12- and 24-month-old anima ls. These data suggest that using a membrane system to assess age-rela ted changes in beta-adrenergic responsiveness in vascular smooth muscl e does not retain the robust differences seen in whole vessels. (C) 19 98 Published by Elsevier Science Ireland Ltd. All rights reserved.