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Calcium antagonist inhibits glomerular cell apoptosis and injuries of L-NAME exacerbated nephrosclerosis in SHR.

Abstract
Increased apoptosis of glomerular cells, with progression of glomerulosclerosis, overactivity of the renin-angiotensin system and elevation of glomerular pressure, follows chronic nitric oxide synthase (NOS) inhibition in spontaneously hypertensive rats (SHR). To gain insight into the regulation of glomerular cell apoptosis in severe nephrosclerosis, we investigated apoptosis, the expression of proliferative cell nuclear antigen (PCNA) in glomeruli, and glomerular morphometric changes in 20-week-old SHR, SHR treated with NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 80 mg/l in drinking water), and SHR treated with L-NAME and the calcium antagonist, efonidipine (20 mg/kg per day), for 3 weeks. Apoptosis in non-sclerotic glomeruli was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. The increase in systolic blood pressure and the severe proteinuria with severe nephrosclerosis induced by chronic NOS inhibition were completely prevented by efonidipine. Furthermore, the glomerular area and capillary tuft area were markedly increased in rats treated with efonidipine compared with both control rats (+30 and +42%, respectively, p<0.01) and rats treated with L-NAME (+35 and +56%, respectively, p<0.01)-treated rats. This calcium antagonist also significantly inhibited the both increases of the glomerular cell apoptosis index (-72%) and the PCNA index (+44%), therefore the alteration between apoptosis and proliferation slightly increased the number of glomerular cells (subcapsular, +22%, p<0.01; juxtamedullary, +2%, not significant). Thus, the calcium antagonist efonidipine seems to play an important role in the regulation of apoptosis and proliferation of glomerular cells and may be effective in preventing nephrosclerosis exacerbated by NOS inhibition.
AuthorsS Watanabe, H Ono, T Ishimitsu, H Matsuoka, Y Ono, T Fujimori
JournalHypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 23 Issue 6 Pg. 683-91 (Nov 2000) ISSN: 0916-9636 [Print] England
PMID11131282 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium Channel Blockers
  • Dihydropyridines
  • Enzyme Inhibitors
  • Nitrophenols
  • Organophosphorus Compounds
  • Proliferating Cell Nuclear Antigen
  • efonidipine
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Apoptosis (drug effects)
  • Calcium Channel Blockers (pharmacology)
  • Cell Count
  • Dihydropyridines (pharmacology)
  • Enzyme Inhibitors (pharmacology)
  • Kidney Glomerulus (drug effects, pathology, physiopathology)
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Nephrosclerosis (pathology)
  • Nitrophenols
  • Organophosphorus Compounds (pharmacology)
  • Proliferating Cell Nuclear Antigen (metabolism)
  • Rats
  • Rats, Inbred SHR (physiology)

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