Age-related changes in P2-purinergic receptors on vascular smooth muscle and endothelium.

The present study examined age-related changes in the vascular relaxation response to adenine nucleotides in hypertensive and normotensive rats. Aortic ring segments from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), age 4-6, 9-10, and 13-14 weeks, were examined for relaxation to adenosine 5'-triphosphate (ATP). The extent of ATP-induced relaxation in aortic ring segments with intact endothelium was unchanged with advancing age. Rubbed (endothelium-denuded) ring preparations at the age of 4-6 weeks showed a dose-dependent relaxation similar to that of the unrubbed rings. With advancing age, the ATP-induced relaxation in the rubbed rings decreased and was abolished. The relaxation response did not differ between the SHR and WKY animals at any age, whether the preparations were rubbed or unrubbed. The stable ATP analogue beta,r-methylene ATP induced a relaxation response similar to ATP in rubbed rings at 4-6 weeks of age. In addition, treatment with 8-phenyltheophylline did not diminish the relaxation induced by ATP. ATP-induced relaxation may be manifested via the direct action on the vascular smooth muscle in young rats and may be altered through the response mediated by endothelium with advancing age. This suggests that the vascular smooth muscle of young rats has a P2-purinergic receptor leading to relaxation and that this receptor activity declines with advancing age. In contrast, a P2-purinergic receptor leading to the generation of endothelium-derived relaxing factor may be activated in endothelial cells with advancing age. The alterations with age of P2-purinergic receptor in the vascular smooth muscle and endothelial cell are not affected by genetic hypertension.