Cardiovascular and renal effects of low-dose atrial natriuretic peptide in compensated cirrhosis.
OBJECTIVE
Patients with cirrhosis and ascites have high plasma levels of atrial natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences cardiovascular homeostasis and renal function in patients with compensated cirrhosis at plasma levels comparable to those observed in patients with cirrhosis and ascites.


METHODS
Radionuclide angiocardiography was performed in eight compensated cirrhotic patients during placebo (three periods of 15 min each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with appropriate blood and urine sampling, to evaluate left ventricular diastolic, systolic, and stroke volume, heart rate, cardiac output, arterial pressure, peripheral vascular resistance, creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone, norepinephrine and hematocrit.


RESULTS
The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L) comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/ L). This increment was associated with significant reductions in left ventricular end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/- 9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased. Peripheral vascular resistance did not change. These hemodynamic effects occurred despite significant increases in plasma renin activity and norepinephrine. ANP also induced increases in creatinine clearance, urinary sodium excretion, and fractional sodium excretion.


CONCLUSIONS
Low-dose ANP affected cardiovascular homeostasis and renal sodium handling in compensated cirrhosis, suggesting that this hormone may be involved in the pathophysiology of systemic hemodynamic and renal functional abnormalities of cirrhosis.
La Villa
G
G
Istituto di Medicina Interna, Dipartimento di Fisiopatologia Clinica, University of Florence School of Medicine, Italy.
Lazzeri
C
C
Pascale
A
A
Sestini
S
S
Bisi
G
G
Sciagrà
R
R
Vecchiarino
S
S
Raggi
V C
VC
Barletta
G
G
Laffi
G
G
Gentilini
P
P
D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D001201:Ascites / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D008875:Middle Aged; D009318:Natriuresis; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood
D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D012083:Renin; D006152:Cyclic GMP; D009638:Norepinephrine