Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist |
| |
Authors: | K Sakamoto Dr R Kikkawa M Haneda Y Shigeta |
| |
Institution: | (1) The Third Department of Medicine, Shiga University of Medical Science, Otsu, 520-21 Shiga, Japan |
| |
Abstract: | Summary The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP.Abbreviations ANP
Atrial natriuretic peptide
- GFR
glomerular filtration rate
- RPF
renal plasma flow
- PAH
para-aminohippurate |
| |
Keywords: | Diabetic nephropathy atrial natriuretic peptide atrial natriuretic peptide receptor antagonist glomerular hyperfiltration |
本文献已被 SpringerLink 等数据库收录! |
|