title: Renal effects of adenosine A1-receptor blockade with 8-cyclopentyl-1,3-dipropylxanthine in hypoxemic newborn rabbits.
abstract: The key role of intrarenal adenosine in mediating the hypoxemic acute renal insufficiency in newborn rabbits has been well demonstrated using the nonspecific adenosine antagonist theophylline. The present study was designed to define the role of adenosine A1 receptors during systemic hypoxemia by using the specific A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Renal function parameters were assessed in 31 anesthetized and mechanically ventilated newborn rabbits. In normoxia, DPCPX infusion induced a significant increase in diuresis (+44%) and GFR (+19%), despite a significant decrease in renal blood flow (RBF) (-22%) and an increase in renal vascular resistance (RVR) (+37%). In hypoxemic conditions, diuresis (-19%), GFR (-26%), and RBF (-35%) were decreased, whereas RVR increased (+33%). DPCPX administration hindered the hypoxemia-induced decrease in GFR and diuresis. However, RBF was still significantly decreased (-27%), whereas RVR increased (+22%). In all groups, the filtration fraction increased significantly. The overall results support the hypothesis that, in physiologic conditions, intrarenal adenosine plays a key role in regulating glomerular filtration in the neonatal period through preferential A1-mediated afferent vasoconstriction. During a hypoxemic stress, the A1-specific antagonist DPCPX only partially prevented the hypoxemia-induced changes, as illustrated by the elevated RVR and drop in RBF. These findings imply that the contribution of intrarenal adenosine to the acute adverse effects of hypoxemia might not be solely mediated via the A1 receptor.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Lausanne University Medical Center, CH 1011 Lausanne, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Prévot
authors.forename: Dolores
authors.initials: D
authors.lastname: Mosig
authors.forename: Mariette
authors.initials: M
authors.lastname: Rijtema
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guignard
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D007668:Kidney / Q000502:physiology*; D011817:Rabbits; D011897:Random Allocation; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014970:Xanthines / Q000378:metabolism*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine