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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Diabetic nephropathy ; atrial natriuretic peptide ; atrial natriuretic peptide receptor antagonist ; glomerular hyperfiltration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Aldose reductase inhibitor ; streptozotocin-diabetic rats ; sciatic nerve sorbitol ; red cell sorbitol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary A new aldose reductase inhibitor, (E)-3-carboxy-methyl-5-[(2E-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) was administered orally to streptozotocin-diabetic rats (60 mg/kg IV) for 14 days and its effect on motor nerve conduction velocity studied. The compound significantly improved motor nerve conduction velocity of diabetic rats at a minimal dose of 10 mg · kg-1 · day-1 (treated 28.8±0.5 versus untreated 23.2±4.7 m/s, p 〈 0.01). The sorbitol content of the sciatic nerve and red blood cells measured after 2 weeks was concomitantly reduced in ONO-2235-treated rats (sciatic nerve: 120±13 versus 595±146 nmol/g wet weight; red blood cell: 91±21 versus 165±39 nmol/g haemoglobin; p 〈 0.01 in both 20 mg · kg-1 · day-1-treated versus untreated animals). These results suggest that sorbitol accumulation might contribute to the development of peripheral nerve dysfunction in acutely diabetic animals and the new aldose reductase inhibitor could be a potential drug for therapy of diabetic neuropathy.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Key words Diabetic nephropathy ; atrial natriuretic peptide ; atrial natriuretic peptide receptor antagonist ; glomerular hyperfiltration.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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. [Diabetologia (1995) 38: 536–542]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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