Atrial natriuretic peptide increases urinary albumin excretion in men with type 1 diabetes mellitus and established microalbuminuria.
Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l-1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg-1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9% saline), low dose (2.5 pmol kg-1 min-1) or high dose (5.0 pmol kg-1 kg min-1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) micrograms min-1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) micrograms min-1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) micrograms min-1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM.
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, UK.
N
N
Prasad
P B
PB
Clarkson
T M
TM
MacDonald
M
M
Ryan
A D
AD
Struthers
C J
CJ
Thompson
D000328:Adult; D000419:Albuminuria / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
D009320:Atrial Natriuretic Factor; D006442:Glycated Hemoglobin