Acute renal hemodynamic effects of ACE inhibition in diabetic hyperfiltration: Role of kinins

R. Komers, M. E. Cooper

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Abstract

Angiotensin converting enzyme (ACE) inhibitors not only reduce angiotensin II (ANG II) levels but also inhibit kinin degradation. The relative roles of ANG II and bradykinin in the acute action of ACE inhibitors on renal hemodynamic parameters in rats after 3 wk of diabetes were explored using antagonists of the ANG II type 1 (AT1) and the bradykinin B2 receptors. Conscious control and streptozotocin diabetic male Sprague-Dawley rats were randomized to receive vehicle, the ACE inhibitor, ramiprilat, the B2- receptor blocker, HOE-140, the AT1-receptor blocker, valsartan, or the combination of ramiprilat and HOE-140. Systolic blood pressure, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction and urinary flow, and sodium excretion were assessed before and during treatment. Diabetic animals had higher GFR and a tendency toward increased RPF and filtration fraction compared with control animals. Acute ramiprilat infusion decreased GFR significantly in diabetic but not in control animals. Valsartan and the combination of ramiprilat and HOE-140 reduced blood pressure to a similar degree to ramiprilat alone, yet did not reduce GFR. No decrease in GFR was observed in any control rat groups. Ramiprilat decreased RPF in diabetic rats but increased RPF in control rats. No such effects on RPF were observed with valsartan. HOE-140 alone did not influence any renal parameter in the diabetic rats. Diabetic rats had increased urinary flow and sodium excretion, but these parameters were not influenced by any drug regimen. In summary, the effects of acute ACE inhibition in reducing diabetic hyperfiltration could be attenuated by concomitant bradykinin receptor blockade and could not be reproduced by the AT1-receptor blocker, valsartan. These findings suggest that kinins play an important role in mediating the acute renal hemodynamic effects of ACE inhibitors in experimental diabetes.

Original languageEnglish (US)
Pages (from-to)F588-F594
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume268
Issue number4 37-4
StatePublished - Jan 1 1995

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Keywords

  • HOE-140
  • angiotensin II
  • diabetes
  • kidney
  • ramipril
  • valsartan

ASJC Scopus subject areas

  • Physiology

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