Early endothelial dysfunction following renal mass reduction in rats

S. Benchetrit, J. Green, D. Katz, J. Bernheim, Mauro Rathaus

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Endothelial dysfunction has been previously described in severely hypertensive rats with renal mass reduction (RMR) receiving large dietary Na loads. Because hypertension and Na loading reduce endothelium-dependent vasodilation, the effect of renal failure per se is unclear. Methods: Responses to acetylcholine in noradrenaline-contracted isolated perfused mesenteric arteries were studied. Vessels were obtained from RMR rats kept on a normal diet, 3 and 10 days after surgery, and the results were compared with those from sham-operated rats (SN). The role of three putative mediators of endothelium-dependent 5 vasodilation was assessed using: L-NAME (10-4 mol L-1); indomethacin (INDO, 10-5 mol L-1); and a mixture of charybdotoxin and apamin (C/A, both 10-7 mol L-1), inhibitors of Ca-activated K-channels to mediate the effects of endothelium-derived hyperpolarizing factor (EDHF). Results: Response to acetylcholine but not that to nitroprusside (endothelium-independent) was decreased in RMR. L-NAME reduced further acetylcholine relaxations in SN but not in RMR. By contrary, INDO decreased acetylcholine vasodilation in RMR but had no effect in SN. C/A had similar effects in the SN and RMR rats. The levels of 6-keto prostaglandin were elevated in the urine of the RMR rats and were perfusate from the F RMR vessels. Conclusion: Endothelial dysfunction occurs early after RMR, even when systolic blood pressure is only minimally elevated and Na intake is normal. This alteration may be because of decreased availability of nitric oxide, partially compensated by increased prostacyclin production.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalEuropean Journal of Clinical Investigation
Volume33
Issue number1
DOIs
StatePublished - 2003

Keywords

  • EDHF
  • Hypertension
  • Nephrectomy
  • Nitric oxide
  • Prostacyclin

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