Cardiac effects of endothelin-1 (ET-1) and related C-terminal peptide fragment: increased inotropy or contribution to heart failure?

Title:

Cardiac effects of endothelin-1 (ET-1) and related C-terminal peptide fragment: increased inotropy or contribution to heart failure?

Creator:

Ján Dřímal, Knezl, V., Dřímal, J., Dřímal, D., Bauerová, K., Viktor Kettmann, Doherty, A. M., and Štefek, M.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:410ff55f-269e-4aeb-81d6-daa447b85cfb
uuid:410ff55f-269e-4aeb-81d6-daa447b85cfb
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, endotel, fyziologie, endothelium, physiology, endothelin-1, ETA and ETB receptors, endothelin antagonicst, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

The contrasting pattern of cardiac inotropy induced by human peptide endothelin-1 (ET-1) has not been satisfactorily explained. It is not clear whether ET-1 is primarily responsible for increased myocardial ET-1 expression and release with resultant inotropic effects, or for the induction of myocardial hypertrophy and heart failure. There are at least two subtypes of endothelin receptors (ETA and ETB) and the inotropic effects of ET-1 differ depending on the receptor involved. Along with some other groups, we reported significant subtype-ETB endothelin receptor down-regulation in human cardiac cells preincubated with endothelin agonists (Dřímal et al. 1999, 2000). The present study was therefore designed to clarify the subtype-selective mechanisms underlying the inotropic response to ET-1 and to its ETB-selective fragment (8-21)ET-1 in the isolated rat heart. The hearts were subjected to (1-21)ET-1 and to (8-21)ET-1, or to 30 min of stop-flow ischemia followed by 40 min of reperfusion, both before and after selective blockade of endothelin receptors.The present study revealed that both peptides, ET-1 and its (8-21)ET-1 fragment, significantly reduced coronary blood flow in nmolar and higher concentrations. The concomitant negative inotropy and chronotropy were marked after ET-1, while the infusion of the ET-1(8-21) fragment produced a slight but significant positive inotropic effect. Among the four endothelin antagonists tested in continuous infusion only the non-selective PD145065 and ETB1/B2-selective BQ788 (in mmolar concentrations) slightly reduced the early contractile dysfunction of the heart induced by ischemia, whereas ETA-selective PD155080 partially protected the rat heart on reperfusion., J. Dřímal, V. Knezl, J. Dřímal Jr , D. Dřímal, K. Bauerová , V. Kettmann, A.M. Doherty , M. Štefek., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2003 Volume:52 | Number:6

Harvested from:

CDK

Metadata only:

false