[Neurohumoral activation, regulation of sodium excretion and vasodilator treatment in heart insufficiency].
BACKGROUND
The benefits of vasodilator therapy guided by hemodynamic goals in patients with severe heart failure (HF) are well documented. Nevertheless, therapy induced arterial underfilling may activate compensatory neurohumoral mechanisms and sodium retention.


OBJECTIVE
To evaluate the effect of vasodilator therapy on neurohumoral activation and sodium excretion in severe HF patients submitted to tailored therapy guided by hemodynamic parameters.


METHODS
Ten male patients (aged 70.2 +/- 2.9 years) with severe HF (left ventricle ejection fraction = 15.2 +/- 1.1%) were evaluated according to hemodynamic parameters and plasma levels of brain natriuretic peptide (BNP), norepinephrine, aldosterone, plasma renin activity (PRA), sodium and creatinine and urinary levels of sodium and creatinine, prior to beginning of nitroprusside therapy, every six hours thereafter (for 24 hours) and again after five days of inhibition of angiotensin converting enzyme (ACE) with lisinopril.


RESULTS
Nitroprusside therapy caused marked increase in cardiac index and substantial reduction in systemic vascular resistance index. Plasma levels of BNP failed significantly while those of PRA, aldosterone and norepinephrine markedly rose, causing substantial reduction of sodium urinary excretion. There were no changes in renal function. Following ACE inhibition by lisinopril, BNP and sodium plasma levels rose, but BNP values remained significantly lower than the initial ones. Norepinephrine and aldosterone returned to base levels and PRA rose sharply. There was an intense natriuretic response and significant elevation of urinary volume. Urinary creatinine and creatinine clearance decreased non-significantly.


CONCLUSIONS
Our results show that intensive vasodilator therapy in patients with severe HF improves hemodynamic parameters and causes activation of renin-angiotensin-aldosterone and adrenergic systems, resulting in sodium retention. Nevertheless, this neurohumoral activation is reversed by ACE inhibitors, thus supporting the "wide spectrum" neurohumoral modulation role attributed to these drugs.
Pimenta
Joana
J
Serviço de Medicina B, Hospital S. João, Unidade de Investigação e Desenvolvimento Cardiovascular do Porto, Porto. joanapimenta@clix.pt
Pereira
Margarida
M
Castro
Alice
A
Dias
Paula
P
Azevedo
Ana
A
Bettencourt
Paulo
P
Ferreira
António
A
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009599:Nitroprusside / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D009599:Nitroprusside; D012964:Sodium; D003404:Creatinine; D017706:Lisinopril