Carvedilol improves uptake-1 in patients with systolic congestive heart failure.

Background: The sympathetic nervous system (SNS) of the whole body, including cardiac sympathetic nerves, is activated in patients with severe congestive systolic heart failure (CHF). Carvedilol can improve clinical status in such patients. This study aimed to determine how carvedilol acts on the SNS to improve CHF. Methods and Results: Ten subjects (New York Heart Association criteria III) were treated using carvedilol at 2.5 mg/d for 1 week. Before and after treatment, subjects walked on a treadmill for 6 minutes, and plasma concentrations of carvedilol, norepinephrine, and 3,4-dihydroxyphenyl glycol were measured. After treatment, norepinephrine was decreased at rest (3.2 +/- 0.3 pmole/mL to 2.1 +/- 0.4 pmole/mL, P < 0.05), while standing (5.4 +/- 1.2 to 3.3 +/- 0.7 pmole/mL, P < 0.01) and during exercise (6.5 +/- 1.3 pmole/mL to 5.1 +/- 1.1 pmole/mL, P < 0.05). Regression lines for percentage changes in norepinephrine and 3,4-dihydroxyphenyl glycol were compared before and after treatment, showing steeper slopes after treatment (P < 0.05). Plasma carvedilol concentrations (1.8 +/- 0.3 ng/mL) did not reach beta-adrenoceptor-blocking levels of effect. Conclusions: Carvedilol is considered to improve function of uptake-1 for the whole-body SNS, including the cardiac SNS, and does not seem to block adrenoceptors at such low doses in CHF patients. However, both effects seem to work at high doses in clinical settings.