Functional heterogeneity of endothelial P2 purinoceptors in the cerebrovascular tree of the rat

The effects of stimulating P2Y(1) or P2Y(2) purinoceptors on the endotheliu m of isolated middle cerebral arteries (MCAs), third-order branches of the MCA (bMCAs), and penetrating arterioles (PAs) of the rat were studied. Afte r pressurization and development of spontaneous tone (25% contraction), res ting diameters for MCAs, bMCAs, and PAs were 203 +/- 5 (n = 50), 99 +/- 2 ( n = 42), and 87 +/- 2 pm (n = 53), respectively. Luminal application of the P2Y(1)-selective agonist 2-methylthioadenosine 5'-triphosphate elicited do se-dependent dilations (or loss of intrinsic tone) in MCAs but not in bMCAs or PAs. The dilation in MCAs was completely blocked by removal of the endo thelium or by nitro-L-arginine methyl ester (10(-5) M), an inhibitor of NO synthase. Luminal application of the P2Y(2)-selective agonist ATP elicited dilations in MCAs, bMCAs, and PAs. Removal of the endothelium abolished the dilations in all vessel groups. Dilations in MCAs have been shown to invol ve both NO and endothelium-derived hyperpolarizing factor (EDHF). The dilat ions in bMCAs and PAs had a minor NO component and prominent EDHF component ; that is, 1) the dilations to ATP were not diminished by the combined inhi bition of NO synthase and cyclooxygenase, 2) the dilations were accompanied by significant hyperpolarizations of the vascular smooth muscle (similar t o 15 mV), and 3) the dilations were completely abolished by the calcium-act ivated potassium channel blocker charybdotoxin. We concluded that the role of NO in purinoceptor-induced dilations diminishes along the cerebrovascula r tree in the rat, whereas the role of EDHF becomes more prominent.