The relative contribution of atrial natriuretic peptide (ANP) and vasodilatory prostaglandins to hyperfiltration in Wistar rats with experimental diabetes was studied 6–8 wk after streptozocin injection. Plasma levels of immunoreactive ANP were significantly higher (P < 0.01) in hyperglycemic diabetic (72.9 ± 11.7 pg/ml) than in normoglycemic diabetic (44.8 ± 8.6 pg/ml) or nondiabetic (40.0 ± 6.8 pg/ml) rats. Blocking endogenous ANP by specific ANP-antiserum infusion reduced significantly (P < 0.01) glomerular filtration rate (GFR) and renal plasma flow (RPF) of hyperglycemic rats compared with preinfusion values (1.23 ± 0.06–1.02 ± 0.04; 2.87 ± 0.25–2.40 ± 0.10 ml · min−1 · 100 g−1, respectively). However, correction of hyperfiltration and hyperperfusion was only partial (nondiabetic rats GFR 0.85 ± 0.07; RPF 2.27 ± 0.13 ml · min−1 · 100 g−1). Because diabetic rats with hyperglycemia also had an increased urinary excretion of prostacyclin metabolite 6-keto–prostaglandin F1α (220.6 ± 62.8 ng/24 h) compared with nondiabetic rats (51.2 ± 2.7 ng/24 h), we wondered whether excessive prostacyclin formation contributed to hyperfiltration and hyperperfusion in this setting. Indomethacin infusion partially reduced GFR (1.25 ± 0.07 to 1.06 ± 0.07 ml · min−1 · 100 g−1 P < 0.05) and RPF (2.85 ± 0.11 to 2.46 ± 0.12 ml · min−1 · 100 g−1 P < 0.01) in diabetic rats. The combined infusion of ANP antiserum and indomethacin normalized GFR and RPF in diabetic rats with hyperglycemia (1.27 ± 0.05 to 0.88 ± 0.05 and 2.84 ± 0.10 to 2.22 ± 0.06 ml · min−1 · 100 g−1, respectively; P < 0.01). This study documents that in experimental diabetic rats with hyperglycemia, increased ANP and prostacyclin act synergistically in mediating the increased GFR and RPF.
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Original Articles|
April 01 1992
Atrial Natriuretic Peptide and Prostacyclin Synergistically Mediate Hyperfiltration and Hyperperfusion of Diabetic Rats
Norberto Perico;
Norberto Perico
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Ariela Benigni;
Ariela Benigni
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Maurizio Gabanelli;
Maurizio Gabanelli
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Antonella Piccinelli;
Antonella Piccinelli
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Marek Ròg;
Marek Ròg
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Carlo De Riva;
Carlo De Riva
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Giuseppe Remuzzi
Giuseppe Remuzzi
Mario Negri Institute for Pharmacological Research and Division of Nephrology, Ospedali Riuniti Bergamo
Bergamo, Italy
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Address correspondence and reprint requests to Giuseppe Remuzzi, MD, Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11–24100 Bergamo, Italy.
Diabetes 1992;41(4):533–538
Article history
Received:
July 22 1991
Revision Received:
December 18 1991
Accepted:
December 18 1991
PubMed:
1535057
Citation
Norberto Perico, Ariela Benigni, Maurizio Gabanelli, Antonella Piccinelli, Marek Ròg, Carlo De Riva, Giuseppe Remuzzi; Atrial Natriuretic Peptide and Prostacyclin Synergistically Mediate Hyperfiltration and Hyperperfusion of Diabetic Rats. Diabetes 1 April 1992; 41 (4): 533–538. https://doi.org/10.2337/diab.41.4.533
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