title: Chronic renal denervation increases renal tubular response to P2X receptor agonists in rats: implication for renal sympathetic nerve ablation.
abstract: BACKGROUND
  Kidney noradrenergic innervation regulates tubular function. Adenosine triphosphate (ATP)-a co-transmitter of norepinephrine-acts on purinoceptors, including ion channel receptor, P2X. P2X receptor agonists, α,β-methylene ATP (α,β-meATP) and β,γ-methylene ATP (β,γ-meATP), induce natriuresis. Regarding the functional co-localization of adrenoceptors and P2X receptors, we evaluated rat renal tubular system sensitivity to natriuretic action of P2X receptor agonists in chronically denervated kidney.
  
  
  METHODS
  Clearance studies with α,β-meATP and β,γ-meATP (intravenous infusion rate, 2 µmol/kg + 20 nmol/kg/min) were performed after bilateral surgical kidney denervation (DNx) and sham-operation (Sham). Na/K-ATPase activity was measured in isolated rat renal proximal tubules.
  
  
  RESULTS
  In DNx compared with Sham, saline infusion significantly increased renal sodium and urine excretion and P2X receptor agonist infusion was significantly more natriuretic and diuretic. In DNx and Sham, respectively, α,β-meATP increased fractional excretion of sodium (FE(Na)) by 2 ± 0.3 and 0.6 ± 0.1% and urine (FE(V)) by 1.6 ± 0.3 and 0.9 ± 0.2%; β,γ-meATP had similar effects. In both groups of rats, natriuretic and diuretic actions were abolished by P2 receptor blocker (pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate, PPADS), mean arterial blood pressure and glomerular filtration rate remained unchanged during infusion of P2X receptor agonists and antagonist and basal Na/K-ATPase activities in isolated proximal tubules were similar. Both α,β-meATP and β,γ-me-ATP decreased the Na/K-ATPase activity, with 20% inhibition (P < 0.05) in denervated and innervated rats; these inhibitory effects were abolished in the presence of PPADS.
  
  
  CONCLUSIONS
  Decreased renal sympathetic activity enhances the natriuretic effect of P2X receptor stimulation. This effect is probably not related to altered Na/K-ATPase activity in renal proximal tubules.
authors.affiliation: Department of Therapy Monitoring and Pharmacogenetics, Medical University of Gdańsk, Gdańsk, Poland. majank@gumed.edu.pl
authors.forename: Robert
authors.initials: R
authors.lastname: Kowalski
authors.forename: Ewelina
authors.initials: E
authors.lastname: Kreft
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kasztan
authors.forename: Maciej
authors.initials: M
authors.lastname: Jankowski
authors.forename: Miroslawa
authors.initials: M
authors.lastname: Szczepanska-Konkel
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058469:Receptors, Purinergic P2X / Q000737:chemistry* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D058469:Receptors, Purinergic P2X; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine