Atrial Natriuretic Peptide and Prostacyclin Synergistically Mediate Hyperfiltration and Hyperperfusion of Diabetic Rats

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 P −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 1α (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 −1 · 100 g −1 P −1 · 100 g −1 , respectively; P