Different Roles for P2Y2 and P2Y6 Receptors in Large and Smaller Coronary Arteries

Abstract

A clear understanding of the physiological regulation of the coronary blood flow is important in order to recognize the changes after a pathological incident, such as a heart attack. Extracellular pyrimidines activate P2Y receptors on both smooth muscle cells and endothelial cells in the vasculature, leading to vasoconstriction and relaxation respectively. The aim of the present study was to examine the receptor profiles along the vasculature, particularly in the coronary circulation. We studied this in arteries utilizing stable pyrimidine analogues and P2Y2 and P2Y6 receptor KO mice in a myograph setup and also performed blood pressure measurements. The results show that P2Y6 mediates most of the UTP and UDP induced contraction in the larger coronary arteries (lumen diameter ~150 µm) and that P2Y2 is an endothelia dependent relaxing receptor. In the smaller coronary arteries (lumen diameter ~ 50 µm) the expression is opposite, with P2Y2 being the contractile receptor and P2Y6 the relaxant receptor, although together with P2Y2. We therefore propose that released UTP can act as a vasodilator downstream of its release, after being degraded to UDP, also without affecting the contractile pyrimidine receptors.The obtained results gives a completely new view of the purinergic regulation in the vascular bed and can be used as an explanation of the many differences in the expression of purinergic receptors both between species and in various arteries.Funding: Lundbeck foundation (R167‐2013‐15379) and Lundbeck Grant of excellence