Aging alters the vascular response to extracellular nucleotides. However, the molecular mechanisms that underlie the effect of aging remain unclear. We investigated the mRNA expression of P2X(1), P2Y(1), P2Y(2) subtypes of the nucleotide receptors (P2) in the basilar artery, aorta and carotid artery from male Sprague-Dawley rats, 2-months and 19-months old. In the basilar arteries of 19-month old rats, as compared to the 2-month old rats, the P2X(1) receptor transcripts were reduced and the P2Y(1) and P2Y(2) receptor mRNA was increased. In the aorta and carotid arteries, P2Y(1) receptor mRNA was decreased in the 19-month old rats when compared to the 2-month old rats. There were no marked changes of P2X(1) and P2Y(2) receptor mRNA between the two age groups in the aorta or carotid artery. In endothelial cells, P2Y(1) and P2Y(2) receptor mRNA was reduced with age. We concluded that, down-regulation of P2X(1) and up-regulation of P2Y(1), P2Y(2) receptor mRNA in smooth muscle cells and down-regulation of P2Y(1) and P2Y(2) receptor mRNA on vascular endothelial cells might underlie the changes of cerebral vascular tone in aging.