title: Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats.
abstract: Renal endothelin-1 (ET-1) and purinergic signaling systems regulate Na(+) reabsorption in the renal medulla. A link between the renal ET-1 and purinergic systems was demonstrated in vitro, however, the in vivo interaction between these systems has not been defined. To test whether renal medullary activation of purinergic (P2) receptors promotes ET-dependent natriuresis, we determined the effect of increased medullary NaCl loading on Na(+) excretion and inner medullary ET-1 mRNA expression in anesthetized adult male Sprague-Dawley rats in the presence and absence of purinergic receptor antagonism. Isosmotic saline (NaCl; 284 mosmol/kgH2O) was infused into the medullary interstitium (500 μl/h) during a 30-min baseline urine collection period, followed by isosmotic or hyperosmotic saline (1,800 mosmol/kgH2O) for two further 30-min urine collection periods. Na(+) excretion was significantly increased during intramedullary infusion of hyperosmotic saline. Compared with isosmotic saline, hyperosmotic saline infused into the renal medulla caused significant increases in inner medullary ET-1 mRNA expression. Renal intramedullary infusion of the P2 receptor antagonist suramin inhibited the increase in Na(+) excretion and inner medullary ET-1 mRNA expression induced by NaCl loading in the renal medulla. Activation of medullary P2Y2/4 receptors by infusion of UTP increased urinary Na(+) excretion. Combined ETA and ETB receptor blockade abolished the natriuretic response to intramedullary infusion of UTP. These data demonstrate that activation of medullary P2 receptors promotes ET-dependent natriuresis in male rats, suggesting that the renal ET-1 and purinergic signaling systems interact to efficiently facilitate excretion of a NaCl load.
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Eman Y
authors.initials: EY
authors.lastname: Gohar
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Speed
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kasztan
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Jin
authors.affiliation: Cardio-Renal Physiology & Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama dpollock@uab.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000096:biosynthesis / Q000502:physiology*; D007679:Kidney Medulla / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009994:Osmolar Concentration; D011188:Potassium / Q000652:urine; D058910:Purinergic P2 Receptor Agonists / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000187:drug effects; D012964:Sodium / Q000378:metabolism / Q000652:urine; D012965:Sodium Chloride / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D058848:Receptors, Purinergic P2X4; D012965:Sodium Chloride; D012964:Sodium; D011188:Potassium; D014544:Uridine Triphosphate
keywords: endothelin-1; inner medulla; kidney; natriuresis; purinergic receptors