title: Regional vascular responses to ATP and ATP analogues in the rabbit kidney in vivo: roles for adenosine receptors and prostanoids.
abstract: OBJECTIVE
  Our knowledge of the effects of P2-receptor activation on renal vascular tone comes mostly from in vitro models. We aimed to characterise the pharmacology of ATP in the renal circulation in vivo.
  
  
  METHODS
  In pentobarbitone anaesthetized rabbits, we examined total renal and medullary vascular responses to ATP (0.2 and 0.8 mg kg(-1)), beta, gamma-methylene ATP (beta, gamma-mATP, 7 and 170 microg kg(-1)), alpha, beta-mATP (0.2 and 2 microg kg(-1)) and adenosine (2 and 6 microg kg(-1)) using transit-time ultrasound and laser Doppler flowmetry, respectively. We also determined whether adenosine receptors, NO or prostanoids contribute to the actions of the purinoceptor agonists.
  
  
  RESULTS
  Renal arterial boluses of ATP, beta,gamma-mATP, and adenosine produced biphasic changes; ischaemia followed by hyperaemia, in total renal and medullary blood flow. alpha,beta-mATP induced only ischaemia. The adenosine receptor antagonist 8-(p-sulphophenyl)theophylline reduced the responses to adenosine and the hyperaemic responses to ATP and beta,gamma-mATP only. NO synthase inhibition (Nomega-nitro-L-arginine) did not significantly alter responses to the P2 receptor agonists. Subsequent cyclooxygenase inhibition (ibuprofen) reduced the ATP- and beta, gamma-mATP-induced increases in renal blood flow. All other responses remained unchanged.
  
  
  CONCLUSIONS
  In the rabbit kidney in vivo, alpha, beta-mATP sensitive receptors mediate vasoconstriction. beta,gamma-mATP and ATP induce vasodilation at least partly through adenosine receptors. ATP induced renal vasodilatation is independent of NO and partly dependent on prostanoids in the bulk of the kidney, but not in the vasculature controlling medullary blood flow.
authors.affiliation: Department of Physiology, Monash University, Melbourne, Victoria, Australia. gabriela.eppel@med.monash.edu.au
authors.forename: G A
authors.initials: GA
authors.lastname: Eppel
authors.forename: S
authors.initials: S
authors.lastname: Ventura
authors.forename: R G
authors.initials: RG
authors.lastname: Evans
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D007672:Kidney Cortex / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D019335:Nitroarginine; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D019001:Nitric Oxide Synthase; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D007052:Ibuprofen