Atenolol improves ventricular function without changing plasma noradrenaline but decreasing plasma atrial natriuretic factor in chronic heart failure
Autonomic and Autacoid Pharmacology
β-blockers; Atrial natriuretic factor; Catecholamines; Heart failure
There is good evidence that β-blockers improve ventricular function, disease progression and survival in patients with left ventricular systolic dysfunction. The aim of this study was to determine the effects of atenolol therapy on the sympathetic nervous system at rest and after ergometric exercise, on left ventricular function and on baseline plasma atrial natriuretic factor (ANF) in ambulatory patients with chronic heart failure (CHF). Twenty-two patients [left ventricular ejection fraction (LVEF) <36%; New York Heart Association II-III] were studied before atenolol treatment. Because of cardiac events (new Hospital admission or death) only 13 patients completed 1 year of treatment. Baseline noradrenaline (NE) concentrations were similar in patients and controls while ANF was higher in patients than in controls (328 ± 35 pg ml-1 vs. 37 ± 3 pg ml-1; P < 0.01). Patients with events showed higher NE (540 ± 87 pg ml--1 vs. 303 ± 44 pg ml-1; P < 0.01) and ANF (460 ± 70 pg ml -1 vs. 291 ± 44 pg ml-1; P < 0.03) at rest; and greater NE response to exercise (2.003 ± 525 pg ml-1 vs. 694 ± 121 pg ml-1; P < 0.005). Atenolol treatment improved LVEF (19.5 ± 1.9% vs. 33 ± 3.9%; P < 0.001), increased exercise tolerance (9 ± 3.2 min vs. 17 ± 4.8 min; P < 0.001) and decreased plasma ANF (292 ± 42 pg ml-1 vs. 133 ± 35 pg ml-1; P < 0.01). Reduced basal dihydroxyphenylglycol (DHPG)/NE ratio (3.4 ± 0.46 vs. 4.3 ± 0.35; P < 0.01) was observed in patients compared with healthy volunteers. Atenolol increased DHPG plasma levels (1.398 ± 129 pg ml-1 vs. 913 ± 86 pg ml-1; P < 0.005) but the DHPG/NE ratio during exercise was not modified after treatment, suggesting that re-uptake of released NE is not changed by β-blocker treatment. In conclusion, the fact that atenolol treatment improves ventricular dysfunction and clinical status without changing plasma NE levels in CHF patients, suggests that plasma NE is a poor surrogate measurement for cardiac sympathetic activity in this pathology. In addition, decrease in plasma ANF produced by atenolol treatment may reflect the improvement of ventricular function.
Gabrielli, O., Puyó, A., De Rosa, A., Armando, I., Barontini, M., & Levin, G. (2002). Atenolol improves ventricular function without changing plasma noradrenaline but decreasing plasma atrial natriuretic factor in chronic heart failure. Autonomic and Autacoid Pharmacology, 22 (5-6). http://dx.doi.org/10.1046/j.1474-8673.2002.00266.x