Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus.
Potential impairment of the efficacy of human atrial natriuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22-37 years). After giving informed consent, patients and eight male control subjects (aged 22-28 years) received in a random double-blind study design i.v. bolus injections of 100 micrograms hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P less than 0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P less than 0.01); hANP resulted in increased plasma protein concentrations only in controls (P less than 0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P less than 0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.
Jungmann
E
E
Zentrum der Inneren Medizin, Johann Wolfgang Goethe-Universität, Frankfurt am Main.
Walter-Schräder
M C
MC
Haak
T
T
Fassbinder
W
W
Wambach
G
G
Althoff
P H
PH
Schöffling
K
K
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004311:Double-Blind Method; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D011897:Random Allocation; D014882:Water-Electrolyte Balance / Q000187:drug effects
D009320:Atrial Natriuretic Factor