DUAL NATRIURETIC PEPTIDE SYSTEM IN EXPERIMENTAL HEART-FAILURE

Objectives. The objectives of this study were 1) to define in an exper imental model of heart failure the time course of changes in plasma br ain natriuretic peptide concentrations during the development of and r ecovery from heart failure, and 2) to relate these changes to changes in atrial natriuretic peptide concentration and hemodynamic status. Ba ckground. Brain natriuretic peptide is a circulating peptide with homo logy to atrial natriuretic peptide. However, unlike the latter, its ch anges during heart failure and its relation to cardiac filling pressur es have not been studied. Methods. Eight male mongrel dogs underwent r ight ventricular pacing at 250 beats/min for 3 weeks until heart failu re occurred and were followed up during recovery for 4 weeks after ces sation of pacing. Results. Heart failure was characterized by an incre ase in both left ventricular end-diastolic pressure (6.6 +/- 4.1 mm Hg at the control measurements to 35.1 +/- 5.9 mm Hg at 3 weeks, p < 0.0 1) and right atrial pressure (6.7 +/- 1.1 to 11.4 +/- 2.1 mm Hg, p < 0 .01). Recovery was accompanied by a return of cardiac filling pressure s to control level. The time course of change of arterial plasma brain natriuretic peptide concentration was similar to that of atrial natri uretic peptide. Plasma concentrations of both peptides increased after 1 week of pacing (16 +/- 4 pg/ml at the control measurement to 59 +/- 20 pg/ml at 1 week, p < 0.001 for brain natriuretic peptide and 84 +/ - 55 to 856 +/- 295 pg/ml, p < 0.001 for atrial natriuretic peptide). The level of both peptides then stayed level with no further increase at 3 weeks and returned to the control value by 4 weeks of recovery. T here was an excellent correlation between plasma concentrations of the two peptides (r = 0.86, p < 0.001) and between the two peptides and c ardiac filling pressures. However, compared with atrial natriuretic pe ptide, plasma brain natriuretic peptide concentration had a smaller pe rcent increase during evolving heart failure and a slower rate of decl ine at recovery. Conclusions. Brain and atrial natriuretic peptide con stitute a dual natriuretic system and are both responsive to changes i n cardiac filling pressures in heart failure. However, brain natriuret ic peptide appears to be less responsive than atrial natriuretic pepti de.