Short-term treatment with ramipril normalizes renal haemodynamics and the natriuretic response to a sodium load in type 1 diabetic patients with early nephropathy.
The objective of the present-study was to determine whether acute inhibition of angiotensin converting enzyme (ACE), normalizes intrarenal sodium handling, renal haemodynamics and renal dopamine output in response to an i.v. NaCl infusion in type 1 diabetic patients with early nephropathy. Nine diabetic patients (aged 28 +/- 3 years) with elevated urinary albumin excretion (173 +/- 39 mg.min-1) were studied. The effects of a 2-hour NaCl infusion (12.5 ml.kg-1-h-1) on para-amino hippuric acid (PAH), insulin, lithium and sodium clearances as well as the urinary dopamine excretion were studied before and after 2 days of acute ACE inhibition. Fifteen healthy subjects (aged 34 +/- 1 years) served as controls. The results showed that 2 days of ACE inhibition improved the natriuretic response significantly (P < 0.05) within the first 2 h following an i.v. NaCl load due to a normalization of the proximal tubular sodium handling. In control subjects urinary dopamine output increased by 14% (P < 0.01) following i.v. NaCl infusion, whereas a blunted increase was seen in the diabetic patients, which tended to normalize following inhibition of ACE. In conclusion, this study demonstrates that patients with type 1 diabetes and early nephropathy display abnormalities in renal haemodynamics, natriuresis and urinary dopamine mobilization in response to a sodium load, which can be reversed by short-term inhibition of ACE.
Stenvinkel
P
P
Department of Renal Medicine, K56, Huddinge University Hospital, Karolinska Institute, Sweden.
Bolinder
J
J
Alvestrand
A
A
D000328:Adult; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004298:Dopamine / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007444:Inulin / Q000493:pharmacokinetics; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D017257:Ramipril / Q000494:pharmacology*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D007444:Inulin; D008094:Lithium; D012964:Sodium; D012083:Renin; D017257:Ramipril; D004298:Dopamine; D010130:p-Aminohippuric Acid