Acute renal hemodynamic effects of ACE inhibition in diabetic hyperfiltration: role of kinins.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Komers
R
R
Department of Medicine, Heidelberg Repatriation Hospital, University of Melbourne, Victoria, Australia.
Cooper
M E
ME
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007705:Kinins / Q000502:physiology*; D008297:Male; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007705:Kinins; D013777:Tetrazoles; C052549:ramiprilat; C065679:icatibant; D000068756:Valsartan; D014633:Valine; D017257:Ramipril; D001920:Bradykinin