Adrenomedullin mediates early phase angiogenesis induced diabetic nephropathy in STZ diabetic rats.

Abstract

OBJECTIVE:

The implication of pro-angiogenic factors including vascular endothelial growth factor (VEGF) and its receptor flk-1 has been reported in diabetic nephropathy as early event. Adrenomedullin (AM), a potent vasodilator peptide, enhances angiogenesis and high levels were seen in diabetic animals and humans. However, its exact role in diabetic nephropathy is unclear. The present study investigated the effects of adrenomedullin receptor antagonist (ADM-52-22) on the early phase angiogenesis-induced diabetic nephropathy.

MATERIALS AND METHODS:

28 male Wistar rats were divided into: 1) Control non-diabetic, 2) Streptozotocin (STZ)-induced diabetic rats (55 mg/kg, i.p.), 3) Control non-diabetic+ADM-52-22, and 4) STZ-diabetes+ADM-52-22 (7 per group). ADM-52-22 was infused for two weeks (250 µg/rat/day, i.p.).

RESULTS:

Diabetes caused an increase in kidney weight, renal VEGF levels, 24 hr urinary protein and nitric oxide excretion and hyperfiltration indicated by creatinine clearance (CrCl). ADM-22-52 reduced the rise in CrCl, total urinary protein and renal hypertrophy in diabetic rats, and attenuated early angiogenic response to diabetes: CD31 staining, flk1 protein and VEGF renal levels.

CONCLUSIONS:

These results show that AM through its receptor mediates early angiogenesis-induced diabetic nephropathy which attributes to the early changes as hyperfiltration and hypertrophy.

• Authors: E A El Eter, A A Al-Masri
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 18 Issue 22 Pg. 3534-43 (Nov 2014) ISSN: 2284-0729 [Electronic] Italy
• PMID: 25491634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Adrenomedullin
• Vascular Endothelial Growth Factor A
• adrenomedullin receptor, rat
• Adrenomedullin
• Streptozocin

Topics

• Adrenomedullin (physiology)
• Animals
• Diabetes Mellitus, Experimental (metabolism, pathology)
• Diabetic Nephropathies (etiology, metabolism, pathology)
• Kidney (drug effects, metabolism, pathology)
• Male
• Neovascularization, Pathologic (metabolism, pathology)
• Rats
• Rats, Wistar
• Receptors, Adrenomedullin (antagonists & inhibitors, physiology)
• Streptozocin
• Vascular Endothelial Growth Factor A (metabolism)