Format

Send to

Choose Destination
Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H1917-26. doi: 10.1152/ajpheart.00258.2008. Epub 2008 Sep 5.

Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes.

Author information

1
Heart Science Centre, National Heart & Lung Institute, Imperial College, London, United Kingdom.

Abstract

Clenbuterol, a compound classified as a beta2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomere shortening, Ca2+ transients, and L-type Ca2+ current and compared these effects to two other clinically used beta2-AR agonists: fenoterol and salbutamol. Clenbuterol (30 microM) produced a negative inotropic response, whereas fenoterol showed a positive inotropic response. Salbutamol had no significant effects. Clenbuterol reduced Ca2+ transient amplitude and L-type Ca2+ current. Selective beta1-AR blockade did not affect the action of clenbuterol on sarcomere shortening but significantly reduced contractility in the presence of fenoterol and salbutamol (P < 0.05). Incubation with 2 microg/ml pertussis toxin significantly reduced the negative inotropic effects of 30 microM clenbuterol. In addition, overexpression of inhibitory G protein (Gi) by adenoviral transfection induced a stronger clenbuterol-mediated negative inotropic effect, suggesting the involvement of the Gi protein. We conclude that clenbuterol does not increase and, at high concentrations, significantly depresses contractility of isolated ventricular myocytes, an effect not seen with fenoterol or salbutamol. In its negative inotropism, clenbuterol predominantly acts through Gi, and the consequent downstream signaling pathways activation may explain the beneficial effects observed during chronic administration of clenbuterol in patients treated with LVADs.

PMID:
18775853
PMCID:
PMC2614565
DOI:
10.1152/ajpheart.00258.2008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center