title: Effects of diadenosine polyphosphates on renal function and blood pressure in anesthetized Wistar rats.
abstract: In this study, the effects of diadenosine polyphosphates on kidney function were examined. Intravenous application of diadenosine hexaphosphate (AP6A) led to a significant threefold increase in both urine flow (from 2.45 +/- 0.2 to 13.8 +/- 0.74 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.41 +/- 0.12 to 1.52 +/- 0.28 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). In contrast, diadenosine triphosphate dose-dependently reduced urine flow (from 3.74 +/- 0.3 to 2.57 +/- 0.1 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.45 +/- 0.1 to 0.13 +/- 0.1 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). ATP and the P2y purinoceptor agonist gamma-S-ATP did not significantly modulate urine flow and Na+ excretion. alpha, beta-methylene-ATP, a P2x purinoceptor agonist, significantly increased urine flow from 1.74 +/- 0.5 to 4.07 +/- 1.51 microL/min per 100 g body wt, whereas Na+ excretion was unaffected. The effects were independent of alterations in GFR. Pretreatment with indomethacin (2.0 mg/kg body wt iv) completely abolished the effects of AP6A on urine flow and Na+ excretion. Similarly, pretreatment with the endothelin antagonist bosentan abolished the effects of AP6A on both urine flow and Na+ excretion, whereas suramin had no effects on the AP6A-induced increase in urine flow. In conclusion, diadenosine polyphosphates exert specific actions on urine flow and Na+ excretion that are different from the effects of ATP. AP6A may partially influence renal function by stimulating prostaglandin and endothelin release.
authors.affiliation: Medizinische Universität-Poliklinik Münster, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hohage
authors.forename: C
authors.initials: C
authors.lastname: Reinhardt
authors.forename: U
authors.initials: U
authors.lastname: Borucki
authors.forename: G
authors.initials: G
authors.lastname: Enck
authors.forename: H
authors.initials: H
authors.lastname: Schlüter
authors.forename: E
authors.initials: E
authors.lastname: Schlatter
authors.forename: W
authors.initials: W
authors.lastname: Zidek
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000077300:Bosentan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D015226:Dinucleoside Phosphates; D016232:Endothelins; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D019001:Nitric Oxide Synthase; D000077300:Bosentan; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin