Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome.
Albuminuria (UAlbV) can be reduced by converting-enzyme inhibitors (CEI), but the hormonal mechanism responsible for this effect has not previously been defined. Since CEI increase kinin activity as well as reduce angiotensin II (ANG II) activity, experiments were performed to determine the effect of isolated alterations in kinin and ANG II metabolism on UAlbV in rats with passive Heymann pephritis. Phosphoramidon was used to potentiate kinin activity without altering ANG II synthesis. Aprotinin was utilized in combination with the CEI, enalapril, to prevent the increase in kinin activity caused by CEI. UAlbV and the fractional renal clearance of albumin (FCAlb) decreased significantly after either phosphoramidon or enalapril, although only enalapril reduced blood pressure. Glomerular filtration rate (GFR) was not affected by either drug. Phosphoramidon did not affect plasma renin activity (PRA) or the pressor response to angiotensin I (ANG I), indicating that ANG II synthesis was not altered. Aprotinin prevented the reduction in UAlbV and FCAlb produced by CEI but not the hypotension, elevated PRA, or ANG I pressor blockade produced by CEI. Aprotinin alone had no effect on UAlbV, GFR, PRA, or blood pressure. UAlbV can be reduced by increasing kinin activity by a mechanism that is not dependent on suppression of ANG II activity or reduction in GFR or blood pressure. CEI may reduce proteinuria as a result of their action on the kallikrein-kinin system rather than on the renin-angiotensin system.
Department of Medicine, Veterans Administration Medical Center, Martinez 94553.
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Hutchison
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Martin
D000419:Albuminuria / Q000652:urine; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D007610:Kallikreins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007705:Kinins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D015260:Neprilysin / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism
D006020:Glycopeptides; D007705:Kinins; D012709:Serum Albumin; D004656:Enalapril; D007611:Aprotinin; D007610:Kallikreins; D012083:Renin; D015260:Neprilysin; C008890:phosphoramidon