Endothelial-mediated dilations of rat middle cerebral arteries by ATP and ADP.
The hypothesis that ATP and ADP produce dilations of rat middle cerebral arteries (MCAs) by different mechanisms was tested. Vessel diameters were measured from pressurized, perfused MCAs after application of different agonists. The luminal administration of ATP and ADP elicited concentration-dependent dilations (35% maximum). Removal of endothelium abolished the dilation to intraluminal ATP and attenuated the dilation to intraluminal ADP. The dilations to ATP were abolished with N omega-nitro-L-arginine methyl ester (L-NAME; 10 microM), a nitric oxide synthase inhibitor, at ATP concentrations of 1 microM and below. However, at concentrations of 10 microM ATP and above, L-NAME had no effect on the response. The dilations to ADP were attenuated by L-NAME to the same degree as removal of endothelium. The mechanism for dilation by ATP was identical to that of UTP, a selective P2u purinoceptor agonist. The mechanism of dilation by ADP was similar to that of 2-methylthioadenosine 5'-triphosphate, a selective P2y purinoceptor agonist. We conclude that ATP and ADP elicit dilations of rat MCA by different mechanisms. ATP and ADP likely stimulate P2u and P2y purinoceptors, respectively.
You
J
J
Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Johnson
T D
TD
Childres
W F
WF
Bryan
R M
RM
D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D058473:Receptors, Purinergic P2Y2; D013872:Thionucleosides / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000227:Adenine Nucleotides; C546387:P2ry2 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D013872:Thionucleosides; C021714:2-methylthioadenosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D000241:Adenosine; D014544:Uridine Triphosphate; D019331:NG-Nitroarginine Methyl Ester