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 album in generally precedes the occurrence of demonstrable loss of glomerula r size-selectivity, However, even in this (microalbuminuric) phase of diabetic nephropathy a defect in glomerular barrier function can be de monstrated during infusion of atrial natriuretic peptide. 2. The aim o f this study was to investigate whether angiotensin-converting enzyme inhibition could prevent the proteinuric response to atrial natriureti c peptide in these patients, We performed infusions of atrial natriure tic peptide (0.01 mu g min(-1) kg(-1)) in 10 patients,vith insulin-dep endent diabetes mellitus and microalbuminuria (urinary albumin excreti on 90 +/- 44 mg/day), both before and after 1 month of treatment with enalapril (20 mg once daily). 3, Despite a 40% reduction in proteinuri a, angiotensin-converting enzyme inhibition did not prevent the atrial natriuretic peptide-induced increase in protein excretion, Both befor e and during angiotensin-converting enzyme inhibition, atrial natriure tic peptide infusion resulted in a significant increase in the fractio nal excretion of large dextran molecules, which is compatible with an increase in flow through large unrestrictive 'shunt' pores, Atrial nat riuretic peptide infusion also induced an increase in the transcapilla ry escape rate of albumin and angiotensin-converting enzyme inhibition also failed to prevent this effect of atrial natriuretic peptide on p eripheral capillary permeability, 4. We conclude that angiotensin-conv erting enzyme inhibition during 1 month does not correct the capillary barrier function defect in patients with diabetes mellitus and microa lbuminuria that is unmasked by atrial natriuretic peptide infusion.