Early impairment of renal hemodynamic reserve in patients with asymptomatic heart failure is restored by angiotensin II antagonism.
BACKGROUND
The early/asymptomatic stages of heart failure (HF) are characterized by sodium retention secondary to derangement of sodium reabsorption at the proximal nephron level. Because this phenomenon is reversed by ACE inhibition, abnormalities of renal sodium handling may depend on intrarenal changes of angiotensin II (AII)/nitric oxide (NO) levels. Renal hemodynamic reserve (ie, the glomerular vasodilatory response to amino acid infusion) has been proposed as a reliable test to assess in vivo AII/NO balance.


RESULTS
In this study, the effects of 6 weeks of treatment with 5 mg/d of enalapril or with 50 mg/d of losartan on systemic hemodynamics and renal function were assessed, at baseline and after amino acid infusion (AA), in patients with mild HF (NYHA class I) and in healthy volunteers. Untreated HF patients showed a basal renal function comparable to that of healthy subjects. After AA, glomerular filtration rate and renal plasma flow significantly increased in healthy subjects (+29.0% and +30.4%, respectively), whereas no vasodilatory response was observed in HF. Although they did not affect basal renal hemodynamics, both enalapril and losartan restored a normal response to AA in HF patients. Blood pressure and heart rate were comparable in HF subjects and healthy subjects at baseline and were not modified by either treatment. Left ventricular ejection fraction was depressed in HF but did not change after either drug. Urinary excretions of cGMP and nitrate (indexes of NO activity in the kidney), comparable in healthy subjects and in HF patients, were unchanged by either enalapril or losartan and did not correlate with renal reserve.


CONCLUSIONS
(1) Renal functional reserve is absent in patients with early/asymptomatic HF and normal renal function and (2) both enalapril and losartan restore a normal vasodilatory response to AA in these patients without affecting basal systemic and renal hemodynamics. These data suggest a major role of AII in the development of early abnormalities in patients with HF.
Magri
P
P
Cattedra di Nefrologia and I Clinica Medica-Università di Napoli Federico II, Italy.
Rao
M A
MA
Cangianiello
S
S
Bellizzi
V
V
Russo
R
R
Mele
A F
AF
Andreucci
M
M
Memoli
B
B
De Nicola
L
L
Volpe
M
M
D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002908:Chronic Disease; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000596:Amino Acids; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D019808:Losartan