BACKGROUND: Microalbuminuria reflects widespread vascular dysfunction in type 1 
diabetes mellitus and results from increased glomerular sieving caused by 
changes in transglomerular pressure and/or permselectivity characteristics of 
the glomerular basement membrane. Increased tubular reabsorption or degradation 
of albumin will offset an early increase in albuminuria. We hypothesized that 
the infusion of atrial natriuretic peptide (ANP) as a tool to increase 
glomerular permeability might uncover changes in permselectivity in patients 
with uncomplicated type 1 diabetes.
METHODS: We investigated whether these patients were characterized by 
endothelial and/or vascular dysfunction. We therefore studied 46 
normoalbuminuric patients (urinary albumin excretion [UAE] < 10 microg/min) with 
type 1 diabetes and 44 healthy controls. Measurements of renal hemodynamics and 
albuminuria were performed before (baseline) and during the infusion of ANP 
(0.01 microg/kg/min). On a separate occasion, endothelial function was assessed 
by the intra-arterial infusion of acetylcholine (ACh), an endothelial-dependent 
vasodilator.
RESULTS: At baseline, glomerular filtration rate (GFR) and effective renal 
plasma flow (ERPF) were greater in patients with diabetes (GFR, 121 +/- 3 versus 
106 +/- 2 mL/min/1.73 m(2); ERPF, 558 +/- 16 versus 527 +/- 13 mL/min/1.73 m(2); 
P < 0.001). The infusion of ANP increased filtration fraction. There were no 
differences in these responses between groups. UAE was significantly greater in 
patients with diabetes after the ANP infusion (15.8 +/- 1.4 [+183%] versus 9.5 
+/- 1.3 microg/min [+96%]; P < 0.01). A subgroup of patients with diabetes with 
an enhanced albuminuric response (change in UAE > 2 SD of controls) to ANP 
infusion (mean UAE, 30.3 +/- 1.0 microg/min; 425% +/- 61%) was characterized by 
a diminished vasodilatory response to ACh (maximal forearm blood flow, 17.2 +/- 
2.9 [+563%] versus 26.3 +/- 2.3 mL/min/dL [+800%] in patients with diabetes with 
a normal albuminuric response; P < 0.05).
CONCLUSIONS: In a subgroup of patients with uncomplicated type 1 diabetes, an 
increase in glomerular permselectivity can be unmasked by the infusion of ANP. 
These patients are characterized by a diminished vascular response to ACh.