title: Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats.
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 less than 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 less than 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 F1 alpha (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 less than 0.05) and RPF (2.85 +/- 0.11 to 2.46 +/- 0.12 ml.min-1.100 g-1, P less than 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 less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Perico
authors.forename: A
authors.initials: A
authors.lastname: Benigni
authors.forename: M
authors.initials: M
authors.lastname: Gabanelli
authors.forename: A
authors.initials: A
authors.lastname: Piccinelli
authors.forename: M
authors.initials: M
authors.lastname: Ròg
authors.forename: C
authors.initials: C
authors.lastname: De Riva
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D004357:Drug Synergism; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013311:Streptozocin
chemical_list: D013311:Streptozocin; D009320:Atrial Natriuretic Factor; D011464:Epoprostenol; D007213:Indomethacin