Angiotensin-converting enzyme inhibition does not correct early defects in renal and vascular permeability in diabetes mellitus.
1. In diabetes mellitus a selective increase in the excretion of albumin generally precedes the occurrence of demonstrable loss of glomerular size-selectivity. However, even in this (microalbuminuric) phase of diabetic nephropathy a defect in glomerular barrier function can be demonstrated during infusion of atrial natriuretic peptide. 2. The aim of this study was to investigate whether angiotensin-converting enzyme inhibition could prevent the proteinuric response to atrial natriuretic peptide in these patients. We performed infusions of atrial natriuretic peptide (0.01 microgram min-1 kg-1) in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (urinary albumin excretion 90 +/- 44 mg/day), both before and after 1 month of treatment with enalapril (20 mg once daily). 3. Despite a 40% reduction in proteinuria, angiotensin-converting enzyme inhibition did not prevent the atrial natriuretic peptide-induced increase in protein excretion. Both before and during angiotensin-converting enzyme inhibition, atrial natriuretic peptide infusion resulted in a significant increase in the fractional excretion of large dextran molecules, which is compatible with an increase in flow through large unrestrictive 'shunt' pores. Atrial natriuretic peptide infusion also induced an increase in the transcapillary escape rate of albumin and angiotensin-converting enzyme inhibition also failed to prevent this effect of atrial natriuretic peptide on peripheral capillary permeability. 4. We conclude that angiotensin-converting enzyme inhibition during 1 month does not correct the capillary barrier function defect in patients with diabetes mellitus and microalbuminuria that is unmasked by atrial natriuretic peptide infusion.
Zietse
R
R
Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Derkx
F H
FH
Weimar
W
W
Schalekamp
M A
MA
D000419:Albuminuria / Q000097:blood / Q000503:physiopathology*; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D002199:Capillary Permeability / Q000187:drug effects*; D003911:Dextrans / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D003911:Dextrans; D007074:Immunoglobulin G; D004656:Enalapril; D009320:Atrial Natriuretic Factor