title: Carvedilol improves uptake-1 in patients with systolic congestive heart failure.
abstract: 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.
  
  
  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 β-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.
authors: Department of Pathophysiology, School of Pharmacy, Hokkaido Pharmaceutical University, Otaru, Hokkaido, Japan.
authors: Maiko
authors: M
authors: Machida
authors: Shigeru
authors: S
authors: Takechi
authors: Tetsuya
authors: T
authors: Fujimoto
authors: Shigeo
authors: S
authors: Kakinoki
authors: Akikazu
authors: A
authors: Nomura
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002227:Carbazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D005080:Exercise Test; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D011412:Propanolamines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011412:Propanolamines; C493227:SLC6A2 protein, human; D000077261:Carvedilol; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine