Early, but not late therapy with a vasopressin V1a-antagonist ameliorates the development of renal damage after 5/6 nephrectomy.

Abstract

INTRODUCTION:

Vasopressin, mainly through the V1a-receptor, is thought to be a major player in the maintenance of hyperfiltration. Its inhibition could therefore lead to a decrease in progression of chronic renal failure. To this end, the effect of the vasopressin V1a-receptor-selective antagonist, YM218, was studied on proteinuria and focal glomerulosclerosis in early and late intervention after 5/6 nephrectomy in rats, and compared with an angiotensin-converting enzyme inhibitor (ACE-I).

MATERIALS AND METHODS:

After 5/6 nephrectomy, early intervention was performed between week 2 and 10 thereafter with the V1a-receptor-selective antagonist (VRA, 10 mg/kg/day, n=10), enalapril (ACE-I, 10 mg/kg/day, n=9), or vehicle (n=8). Late intervention was performed in another group between week 6 and 12 with VRA (10 mg/kg/day, n=7), lisinopril (ACE-I, 5 mg/kg/day, n=7), or vehicle (n=7).

RESULTS:

In early intervention, proteinuria and focal glomerulosclerosis were significantly decreased by VRA compared to vehicle (44+7% and 59+8% respectively). ACE-I significantly decreased proteinuria (67+7%) and a trend towards a decrease in focal glomerulosclerosis was observed (30+18%). In late intervention, VRA did not decrease proteinuria and focal glomerulosclerosis compared to vehicle (21+20% and 0%, respectively), ACE-I significantly lowered proteinuria (92+2%) and a focal glomerulosclerosis (69+1%) lowering trend was observed.

CONCLUSION:

These results indicate that VRA may protect against early progression of renal injury after 5/6 nephrectomy, whereas its effectiveness seems limited in established renal damage.

• Authors: Willemijn A K M Windt, Atsua Tahara, Alex C A Kluppel, Dick de Zeeuw, Robert H Henning, Richard P E van Dokkum
• Journal: Journal of the renin-angiotensin-aldosterone system : JRAAS (J Renin Angiotensin Aldosterone Syst) Vol. 7 Issue 4 Pg. 217-24 (Dec 2006) ISSN: 1470-3203 [Print] England
• PMID: 17347933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4'-(4,4-difluoro-5-(2-oxo-2-(4-piperidinopiperidino)ethylidene)-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl)-2-methyl-3-furanilide
• Angiotensin-Converting Enzyme Inhibitors
• Antidiuretic Hormone Receptor Antagonists
• Benzazepines
• Piperidines
• Enalapril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Antidiuretic Hormone Receptor Antagonists
• Benzazepines (administration & dosage, therapeutic use)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Enalapril (pharmacology)
• Glomerular Filtration Rate (drug effects)
• Glomerulosclerosis, Focal Segmental (drug therapy, physiopathology)
• Kidney (drug effects)
• Male
• Nephrectomy
• Piperidines (administration & dosage, therapeutic use)
• Proteinuria (drug therapy)
• Rats
• Rats, Wistar