Angiotensin-converting enzyme inhibition by quinapril blocks the albuminuric effect of atrial natriuretic peptide in Type 1 diabetes and microalbuminuria.
OBJECTIVE
This study examined the effect of angiotensin-converting enzyme inhibition, administered at doses with no effect on systemic blood pressure, on the albuminuric action of atrial natriuretic peptide (ANP).


METHODS
Seven Type 1 diabetic patients with established microalbuminuria participated in a two limb, single-blind, placebo controlled study. Subjects were administered quinapril 10 mg daily or placebo for 7 days prior to study. On the study day, subjects were euglycaemic clamped and subsequently fluid loaded (20 ml/kg tap water orally plus urinary losses). At steady state diuresis, a 1 h intravenous infusion of ANP 0.05 mg.kg(-1) x min(-1) was administered. Urine was collected at 15-min intervals for estimation of albumin-creatinine ratio (ACR). Results were analysed by ANOVA.


RESULTS
Baseline mean arterial pressure was similar after pre-treatment with quinapril and placebo (98.7 +/- 3.8 vs. 100 +/- 4.5 mmHg, mean +/- SD, P > 0.5), and was unaltered by ANP infusion on either study day. Baseline ACR was similar on quinapril and placebo (P = 0.13). ANP infusion induced a rise in urine ACR with placebo (58.4 +/- 40.2 to 393.6 +/- 262.9 mg/mmol, P = 0.006), but not with quinapril (29.3 +/- 10.7 to 81.5 +/- 43 mg/mmol, P = 0.15). The urine ACR response to ANP infusion was higher with placebo than with quinapril (P = 0.02).


CONCLUSIONS
Quinapril blocks the albuminuric effect of intravenous infusion of ANP in subjects with Type 1 diabetes mellitus and established microalbuminuria. This action is independent of changes in mean arterial pressure and creatinine clearance.
McKenna
K
K
Diabetes Centre, Victoria Infirmary, Glasgow, Scotland.
Smith
D
D
Barrett
P
P
Glenn
A
A
Kesson
C M
CM
Connell
J
J
Thompson
C J
CJ
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000652:urine*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D007546:Isoquinolines / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D010919:Placebos; D000077583:Quinapril; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007328:Insulin; D007546:Isoquinolines; D010919:Placebos; D044005:Tetrahydroisoquinolines; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D000077583:Quinapril