Influence of angiotensin converting enzyme inhibition and angiotensin II type 1 receptor antagonism on renal sodium and water handling and albuminuria during infusion of atrial natriuretic factor into healthy volunteers.
BACKGROUND
Atrial natriuretic factor increases urinary sodium and water excretion. It also causes an increase in albuminuria. Angiotensin converting enzyme inhibition attenuates the effects of atrial natriuretic factor on renal sodium and water handling; however, it is not known whether this effect is mediated by the accompanied decrease in blood pressure or by suppression of the renin-angiotensin system.


OBJECTIVE
To test the hypothesis that atrial natriuretic factor mediates natriuresis and diuresis by inhibiting angiotensin II, by studying the effects of the angiotensin converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan. In addition, the effects of these drugs on atrial natriuretic factor-induced albuminuria were examined.


METHODS
We investigated the effects of enalapril and losartan on atrial natriuretic factor-induced changes in urinary excretion of sodium, water and albumin from eight healthy volunteers. Measurements of systemic and renal haemodynamics in these subjects were performed before and during a 2 h infusion of atrial natriuretic factor [0.01 microg/kg per min (low dose) for the first 60 min and 0.02 microg/kg per min (high dose) for the second 60 min]. Measurements were performed after 5 days of pretreatment with placebo, 50 mg losartan or 20 mg enalapril daily.


RESULTS
Mean arterial pressures during the clearance study were 84.6 +/- 1.7 mmHg after placebo, 84.0 +/- 2.2 mmHg after losartan treatment and 80.0 +/- 2.5 mmHg after enalapril treatment (P < 0.05). Plasma renin activity was significantly increased both by losartan and by enalapril treatments. Neither enalapril nor losartan treatment attenuated atrial natriuretic factor-induced changes in renal haemodynamics. After placebo pretreatment, fractional urinary excretion of sodium increased significantly during infusion of atrial natriuretic factor. Losartan treatment did not influence the increase in urinary excretion of sodium during infusion of atrial natriuretic factor, whereas enalapril treatment significantly attenuated this increase (P < 0.01). Atrial natriuretic factor significantly increased albuminuria. Neither losartan nor enalapril treatment reduced atrial natriuretic factor-induced albuminuria.


CONCLUSIONS
Enalapril treatment lowered blood pressure and attenuated the atrial natriuretic factor-induced increase in urinary excretion of sodium. In contrast, the angiotensin II type 1 receptor antagonist losartan, at a dosage that did not lower blood pressure, did not attenuate the increase in urinary excretion of sodium. These data indicate that atrial natriuretic factor increases natriuresis and diuresis independently of angiotensin II. The increase in albuminuria during infusion of atrial natriuretic factor was not influenced by enalapril and losartan treatments.
Vervoort
G
G
University Hospital Nijmegen, St Radboud, Department of General Internal Medicine, The Netherlands. G.Vervoort@aig.azn.nl
Hertenberg
F
F
Wetzels
J F
JF
Smits
P
P
D000328:Adult; D000419:Albuminuria / Q000139:chemically induced / Q000503:physiopathology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D019808:Losartan / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012079:Renal Circulation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D004656:Enalapril; D009320:Atrial Natriuretic Factor; D019808:Losartan