Possible association of decrease of ATP-induced vascular relaxation with reduction of cyclic GMP during aging.

The effect of aging on the ATP-induced relaxation of rat thoracic aorta was examined. Haemoglobin, methylene blue and NG-nitro L-arginine, and removal of the endothelium inhibited or reversed the relaxation induced by ATP. The relaxant response of the aorta to ATP was greatest in the preparations from 4-week-old rats. As the age of rats increased to 45 and 105 weeks, the concentration-response curve for ATP was shifted to the right with reduction of maximal relaxation. ATP elevated cyclic GMP levels. This action was endothelium-dependent and inhibited by methylene blue, haemoglobin and NG-nitro L-arginine. With an increase in age of the rats from 4 weeks to 45 weeks, ATP-stimulated cyclic GMP production was attenuated, and in the aorta from 105-week-old rats cyclic GMP level was no longer elevated by ATP. In contrast to the age-associated marked change in cyclic GMP levels, cyclic AMP production was not affected by aging. It is suggested that age-related changes in ATP-induced relaxation and cyclic GMP formation occur mainly at the level of the vascular smooth muscle. Alterations in soluble guanylate cyclase, at step(s) distal to the guanylate cyclase, or in cyclic GMP-phosphodiesterase might contribute.