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.
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Abbreviations
- A1:
-
adenosine type 1 receptor
- A2:
-
adenosine type 2 receptor
- A2a/b:
-
adenosine type 2a or type 2b receptor
- DPCPX:
-
8-cyclopentyl-1, 3-dipropylxanthine
- FF:
-
filtration fraction
- MAP:
-
mean arterial blood pressure
- PAH:
-
para-aminohippuric acid
- RBF:
-
renal blood flow
- RVR:
-
renal vascular resistance
- TGF:
-
tubuloglomerular feedback
- UV:
-
urine flow rate
- UNaV:
-
urinary excretion of sodium
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Acknowledgements
The authors thank Mrs. M. Julita and M. Thonney Viani for skillful technical help and their valuable contributions in the laboratory.
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Supported by the Swiss National Science Foundation, grants numbers 3200-036574/92 and 3200-064041.00.
Presented in abstract form at the 12th Congress of the International Pediatric Nephrology Association, Seattle, WA, U.S.A., September 2001, and the 36th Annual Meeting of the European Society for Pediatric Nephrology, Bilbao, Spain, September 2002.
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Prévot, A., Mosig, D., Rijtema, M. et al. Renal Effects of Adenosine A1-Receptor Blockade with 8-Cyclopentyl-1,3-Dipropylxanthine in Hypoxemic Newborn Rabbits. Pediatr Res 54, 400–405 (2003). https://doi.org/10.1203/01.PDR.0000078273.08316.26
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DOI: https://doi.org/10.1203/01.PDR.0000078273.08316.26
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