Differential effects of sulindac on renal hemodynamics and function in the rat

R Kramp, N Caron, J Genard, C Lejeune, E Gulbis, Aline Herman

Research output: Contribution to journalArticlepeer-review

Abstract

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n = 12). In the 5 mg/kg b.w. sulindac group (n = 7), renal blood flow progressively and significantly increased from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n = 5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P <0.025). Also, Na+ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n = 15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P <0.05; n = 6). In conclusion, differential effects of sulindac on renal hemodynamics, Na+ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.
Original languageEnglish
Pages (from-to)165-76
Number of pages12
JournalEuropean Journal of Pharmacology
Volume330
Issue number2-3
Publication statusPublished - 9 Jul 1997

Keywords

  • Renin
  • Renal Circulation
  • Animals
  • Drug Interactions
  • Dose-Response Relationship, Drug
  • Cyclooxygenase Inhibitors
  • Prostaglandins
  • Potassium
  • Water
  • Sodium
  • Rats
  • Proadifen
  • Glomerular Filtration Rate
  • Cytochrome P-450 Enzyme System
  • Rats, Wistar
  • Kidney
  • Anti-Inflammatory Agents, Non-Steroidal
  • Sulindac
  • Arachidonic Acid
  • Male

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