Angiotensin II does not acutely reverse the reduction of proteinuria by long-term ACE inhibition.
Angiotensin converting enzyme (ACE) inhibitors are known to lower urinary protein excretion in human renal disease. This proteinuria lowering effect of ACE inhibition has been hypothesized to be a result of renal hemodynamic changes due to the inhibition of angiotensin II (Ang II) production. To test this hypothesis we studied the short-term effects of different doses of exogenous Ang II (5%, 10% and 20% of the pressor dose) on renal hemodynamics and urinary protein excretion in comparison with placebo infusion in six non-diabetic normotensive proteinuric patients, both before and after three months treatment with the ACE inhibitor, lisinopril. Lisinopril lowered proteinuria from 7.5 +/- 1.9 to 2.7 +/- 0.6 g/24 hr and induced a fall in blood pressure, renal vascular resistance and filtration fraction, whereas plasma Ang II levels were similar to the pre-treatment values. Ang II infusion induced typical effects which appeared to be similar before and during lisinopril treatment: a dose-related fall in renal plasma flow and rise in systemic blood pressure, renal vascular resistance and filtration fraction, while the glomerular filtration rate remained relatively stable. However, neither before nor during lisinopril therapy did any changes in urinary protein loss occur during the infusions of Ang II, despite the fact that Ang II reversed the long-term systemic and renal hemodynamic changes induced by the ACE inhibitor. We conclude that the long-term antiproteinuric effect of the ACE inhibitor, lisinopril, is neither mediated through changes in circulatory Ang II levels nor influenced by acute changes in systemic and renal hemodynamics, suggesting a non-hemodynamic mechanism of action.
Heeg
J E
JE
Department of Medicine, State University Hospital Groningen, The Netherlands.
de Jong
P E
PE
van der Hem
G K
GK
de Zeeuw
D
D
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017706:Lisinopril; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000503:physiopathology; D012079:Renal Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D004656:Enalapril; D017706:Lisinopril