title: Unusual absence of endothelium-dependent or -independent vasodilatation to purines or pyrimidines in the rat renal artery.
abstract: BACKGROUND
  Adenosine triphosphate (ATP) is a cotransmitter with noradrenaline (NA) in sympathetic perivascular nerves. It has a dual role in the maintenance of vascular tone as ATP, released from endothelial cells during shear stress or hypoxia, induces vasodilatation via endothelial P2Y receptors or by direct action on smooth muscle. The role and distribution of P2 receptors is well characterized for many blood vessels but not for the rat renal artery. This study aims to determine whether ATP is a vasoconstrictor cotransmitter with NA and whether ATP induces vasodilatation via the endothelium or smooth muscle.
  
  
  METHODS
  On isolated rat renal arteries, electrical field stimulation (EFS) in the absence and presence of antagonists to P2X receptors and alpha1-adrenoceptors was examined. Concentration-response curves were constructed to NA, ATP, alpha,beta-methylene ATP (alpha,beta-meATP), uridine triphosphate (UTP), and 2-methylthio ADP (2-MeSADP) on low tone. Curves to acetylcholine (ACh), 2-MeSADP, and UTP were constructed on raised tone. Immunofluorescent localization of P2X and P2Y receptor subtypes was performed.
  
  
  RESULTS
  Electrical field stimulation induced vasoconstriction, partially inhibited by the P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, and predominantly by prazosin. Exogenous NA and ATP mimicked EFS; immunostaining for P2X1 and P2X2 receptors was expressed on vascular smooth muscle. Unusually, ATP, 2-MeSADP, and UTP failed to induce vasodilatation. Acetylcholine induced vasodilatation. alpha,beta-meATP, 2-MeSADP, and UTP induced vasoconstriction via P2X1, P2Y1, and P2Y2 receptors, respectively. Immunostaining for P2X1, P2Y1, and P2Y2 receptors was expressed on the vascular smooth muscle.
  
  
  CONCLUSIONS
  Adenosine triphosphate and NA are cotransmitters in sympathetic nerves supplying the rat renal artery, NA being the dominant partner. The novel feature of this vessel is that purines and pyrimidines do not produce either endothelium-dependent or -independent vasodilatation; P2X1, P2Y1, and P2Y2 receptors on the smooth muscle all mediate vasoconstriction.
authors.affiliation: Autonomic Neuroscience Institute, Royal Free and University College Medical School, London.
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Knight
authors.forename: Rachel
authors.initials: R
authors.lastname: Oliver-Redgate
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Burnstock
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology*; D013194:Staining and Labeling; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C546384:P2ry1 protein, rat; C546387:P2ry2 protein, rat; D011687:Purines; D011743:Pyrimidines; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D014662:Vasoconstrictor Agents; D000255:Adenosine Triphosphate; D009638:Norepinephrine