Intrarenal determinants of sodium retention in mild heart failure: effects of angiotensin-converting enzyme inhibition.
The onset and the mechanisms leading to Na+ retention in incipient congestive heart failure (CHF) have not been systematically investigated. To investigate renal Na+ handling in the early or mild stages of CHF, Na+ balance and renal clearances were assessed in 10 asymptomatic patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (HF) off treatment (left ventricular ejection fraction, 29.7+/-2%) and in 10 matched normal subjects during a diet containing 100 mmol/d of NaCl and after 8 days of high salt intake (250 mmol/d). Six patients were studied again after 6 weeks of treatment with enalapril (5 mg/d P.O.). At the end of the high salt diet, in patients with mild HF the cumulative Na+ balance exceeded by 110 mmol that of normal subjects (F=3.86, P<.001). During high salt intake, renal plasma flow and glomerular filtration rate were similarly increased in both normal subjects and mild HF patients. In spite of comparable increases of filtered Na+ in the two groups, fractional excretion of Na+, fractional clearance of free water, and fractional excretion of K+ (indexes of distal delivery of Na+) increased in normal subjects and were reduced in patients with mild HF. During enalapril treatment, in the mild HF patients the cumulative Na+ balance was restored to normal; furthermore, enalapril significantly attenuated the abnormalities in the distal delivery of Na+. Our results indicate that a defective adaptation of Na+ reabsorption in the proximal nephron is associated with Na+ retention in response to increased salt intake in the early or mild stages of HF. These abnormalities of renal Na+ handling are largely reversed by enalapril.
Volpe
M
M
1a Clinica Medica, Universita Federico II, Naples, Italy. volpema@cds.unina.it
Magri
P
P
Rao
M A
MA
Cangianiello
S
S
DeNicola
L
L
Mele
A F
AF
Memoli
B
B
Enea
I
I
Rubattu
S
S
Gigante
B
B
Trimarco
B
B
Epstein
M
M
Condorelli
M
M
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001826:Body Fluids / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004039:Diet, Sodium-Restricted; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D012964:Sodium