Blood pressure reduction initiates the antiproteinuric effect of ACE inhibition.
Several observations question the role of blood pressure and renal hemodynamic changes in the long-term antiproteinuric effect of ACE inhibition. To differentiate blood pressure and renal effects in the initial antiproteinuric response, the placebo-controlled acute effects of the ACE inhibitor enalaprilat (10 mg i.v.) on blood pressure, renal hemodynamics, and proteinuria were compared with those of nitroprusside in nine patient with non-diabetic proteinuria. In addition, we studied whether an exogenous angiotensin II infusion reverse the initial enalaprilat-induced antiproteinuric response. Enalaprilat and nitroprusside reduced MAP by -11.3 +/- 2.4% and -14.1 +/- 2.3%, respectively, whereas only enalaprilat showed renal hemodynamic effects, reflected by an increase in ERPF of 18.4 +/- 5.4% and a decrease in FF of -17.1 +/- 2.6%. Despite the contrasting renal hemodynamic profiles, enalaprilat (-10.6 +/- 4.8%) and nitroprusside (-12.8 +/- 5.1% equally decreased proteinuria. Exogenous infusion of angiotensin II completely reversed the blood pressure reduction and renal efferent vasodilatation induced by enalaprilat. proteinuria also increased by 13.1 +/- 7.8% to placebo level, albeit statistically non-significant. We conclude that the initial antiproteinuric effect of ACE inhibition appears to be mediated by blood pressure reduction and does not require its specific renal hemodynamic effect. Further studies should clarify whether the renal efferent vasodilatation during ACE inhibition is required to gradually induce renal structural changes that prevent the abundant passage of proteins.
Hemmelder
M H
MH
Groningen Institute for Drug Studies (GIDS), Department of Medicine, University Hospital, The Netherlands.
de Zeeuw
D
D
Gansevoort
R T
RT
de Jong
P E
PE
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D015773:Enalaprilat / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000008:administration & dosage*; D011507:Proteinuria / Q000188:drug therapy / Q000503:physiopathology*; D016037:Single-Blind Method; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D015773:Enalaprilat