Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats

Norberto Perico, Ariela Benigni, Maurizio Gabanelli, Antonella Piccinelli, Marek Ròg, Carlo De Riva, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

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 F (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 -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.

Original languageEnglish
Pages (from-to)533-538
Number of pages6
JournalDiabetes
Volume41
Issue number4
Publication statusPublished - Apr 1992

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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