The albuminuric action of atrial natriuretic peptide is not modified by ACE‐inhibition with perindopril in Type 2 diabetes

AIMS: Atrial natriuretic peptide (ANP) increases urine albumin excretion (UAER) in humans with Type 1 diabetes. The aim of this study was to establish if ANP increases UAER in microalbuminuric subjects with Type 2 diabetes and to examine whether the albuminuric action of ANP was inhibited by pre-treatment with the ACE-inhibitor perindopril. METHODS: Seven microalbuminuric, normotensive males with Type 2 diabetes were entered into a randomised, double-blind, three-armed study of (i) intravenous infusion of ANP (0.25 microg/kg/min in 0.9% NaCl) after 3 weeks' pre-treatment with placebo, (ii) intravenous infusion of vehicle (0.9% NaCl only) after 3 weeks' pre-treatment with placebo, or (3) intravenous infusion of ANP (0.25 microg/kg/min in 0.9% NaCl) after 3 weeks' pre-treatment with perindopril, 4 mg daily. RESULTS: Baseline parameters were similar on all three study days. During the placebo/vehicle arm there was no change in urine flow rate (UFR, P=0.61), urine cyclic guanosine monophosphate (UcGMP P=0.48) or UAER (P=0.99). During the placebo/ANP arm there was a rise in UFR [13.7+/-2.8 (mean+/-sd) to 25.7+/-7.7 mL/min, P<0.001], UcGMP (60.0+/-36.6 to 160.8+/-118.5 micromol/mmolCr, P=0.045) and UAER [5.13 [2.4-11.6][median (range)] to 71.6 [21.6-175.1] mg/mmolCr, P<0.001]. Pre-treatment with perindopril did not alter the changes in UFR (P=0.63), UcGMP (P=0.46) or UAER (P=0.99) to infusion of ANP, compared with the placebo/ANP arm. CONCLUSION: ANP increases UAER in microalbuminuric patients with Type 2 diabetes and the albuminuric action of ANP is not inhibited by pre-treatment with the ACE inhibitor perindopril.