The antiproteinuric action of angiotensin-converting enzyme is dependent on kinin.
Converting enzyme inhibitors (CEI) reduce proteinuria in nephrotic humans and animals, but the mediator(s) of this effect has not been identified definitively. To determine whether enhanced kinin activity contributes to the antiproteinuric action of CEI, rats with passive Heymann nephritis were treated with the B2 kinin receptor antagonist HOE 140, 300 micrograms/kg per day, for 3 days and then the CEI enalapril (ENAL), 35 mg/kg per day, was given for another 4 days while HOE 140 was continued (HOE/ENAL). Additional groups of nephrotic rats were untreated (CON), received HOE 140 only (HOE), or received ENAL only. ENAL alone produced a > 60% decrease in albuminuria after 4 days, whereas HOE 140 alone had no effect on albuminuria. In HOE/ENAL, pretreatment with HOE 140 prevented the decrease in albuminuria observed in ENAL. GFR increased significantly over time in all groups but was not different among the groups on any day. The clearance of albumin decreased significantly in ENAL (P < 0.001) and was significantly lower than in CON, HOE, or HOE/ENAL on Day 10. The fractional clearance of albumin decreased in all groups as a result of the increase in GFR but was significantly lower in ENAL compared with the other three groups at Day 10 and was not different between CON, HOE, and HOE/ENAL. Plasma renin activity and concentration were increased significantly in both ENAL and HOE/ENAL, indicating that converting enzyme was effectively inhibited in both groups. It was concluded that enhanced kinin activity contributes to the antiproteinuric action of CEI in this model of nephrotic syndrome.
Hutchison
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FN
Division of Nephrology, Medical University of South Carolina, Charleston, USA.
Cui
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X
Webster
S K
SK
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000097:blood / Q000503:physiopathology / Q000652:urine; D007705:Kinins / Q000502:physiology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology*; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000032:analysis; D013997:Time Factors
D007705:Kinins; D012709:Serum Albumin; D004656:Enalapril; C065679:icatibant; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin