[Effect of digoxin on atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cyclic 3', 5'-guanosine monophosphate (cGMP) in patients with chronic congestive heart failure].
Neurohumoral factors play important role in the pathogenesis of congestive heart failure (CHF) and digoxin (dig) is one of the most frequently used drugs in this condition. The aim of this study was to assess the effects of dig on atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their "second messenger" cyclic 3',5'-guanosine monophosphate (cGMP).


METHODS
The study group consisted of 25 patients (pts) aged 25-81 with CHF (NYHA II/III), 13 women and 12 men. Control group consisted of 10 healthy volunteers, 2 women and 8 men. The blood samples for evaluation of ANP, BNP and cGMP plasma level was taken at baseline conditions and 3 hours (h) after intravenous injection of 0.25 mg of dig. From the next day 0.25 mg dig was administrated orally for 6 days and plasma levels of ANP, BNP and cGMP were assessed on the 3rd and 6th day of treatment. Medium serum dig concentration on the 6th day was 0.98 ng/mL.


RESULTS
The baseline ANP, BNP and cGMP plasma level was significantly higher in pts with CHD than in control group (ANP 144.4 vs 98.8 pg/ml p < 0.001; BNP 130.0 vs 97.2 pg/ml p < 0.001; cGMP 1.44 vs 0.86 pg/ml p < 0.001). In pts with CHF there was a significant increase ANP, BNP and cGMP plasma level 3 h after dig intravenous injection (ANP 205.2 vs 144.4 pg/ml p < 0.01; BNP 227.1 vs 130.0 pg/ml p < 0.01; cGMP 1.84 vs 1.44 pg/ml p < 0.01). The ANP and BNP plasma level after 3 days of oral dig was still significantly increased (ANP 171.1 vs 144.4 pg/ml p < 0.05; BNP 223.7 vs 130.0 pg/ml p < 0.01). ANP, BNP and cGMP plasma level was higher in pts with CHF also after 6 days of oral dig, but the difference was statistically significant. After 6 days of digoxin treatment there was a significant increase of ejection fraction (p < 0.005), with reduction of end-diastolic diameter of left ventricle (p < 0.05) and diameter of left atrium (p < 0.01). ANP at baseline correlated positively with baseline cGMP (r = 0.702 p < 0.05). On the 6th day BNP correlated positively with cGMP (r = 0.628 p < 0.05). 3 h after dig intravenous injection ANP correlated positively with BNP (r = 0.881 p < 0.05), but on the 3rd day of oral dig ANP correlated negatively with BNP (r = -0.536 p < 0.05). On the 6th day of oral dig end-diastolic diameter of left ventricle correlated negatively with BNP (r = -0.483 p < 0.05) and cGMP (r = -0.824 p < 0.05).


CONCLUSIONS
1. In pts with CHF a single intravenous digoxin injection increases ANP, BNP and cGMP plasma level. 2. Oral digoxin administration supports this beneficial neurohumoral effect and improves hemodynamic parameters of left ventricle as well as reduces left atrium diameter.
Kobusiak-Prokopowicz
M
M
Katedra i Klinika Kardiologii AM we Wrocławiu.
Swidnicka-Szuszkowska
B
B
Mysiak
A
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D006152:Cyclic GMP / Q000097:blood*; D004077:Digoxin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D020097:Natriuretic Peptide, Brain; D004077:Digoxin; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP