Although activation of the endothelin (ET) system contributes to pulmonary hypertension, modifications of the cardiopulmonary ET system and its responses to chronic ET receptor blockade are not well known. To investigate this, rats were injected with monocrotaline (60 mg/kg intraperitoneal) or saline, followed with treatment with the selective ETA receptor antagonist LU135252 (LU; 50 mg·kg-1·day-1) or with saline. After 3 weeks, haemodynamics, cardiac hypertrophy, ET-1 levels and cardiopulmonary ET-receptor-binding profile were evaluated. Monocrotaline (n=7) elicited marked pulmonary hypertension and right ventricular hypertrophy compared with controls (n=8). Both variables were substantially attenuated by LU therapy (n=8; P<0.05 for both). After monocrotaline, right ventricular ET-1 levels were more significantly increased than in the left ventricle (+198% compared with +127%; P<0.05). ETB receptor density was augmented (3-fold) in the right ventricle, whereas that of ETA receptors was not affected. LU treatment also significantly attenuated these alterations (P<0.05). In the lungs, ET-1 levels were not increased after monocrotaline, whereas the balance of ETB to ETA receptors was altered, with a trend toward a lower percentage of ETB than in the control rats. LU treatment did not affect these variables in the lungs. Therefore monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy are associated with the up-regulation of ET-1 and ETB receptors in the right ventricle. These alterations are attenuated with the reduction of pulmonary hypertension and right ventricular hypertrophy after chronic blockade of the ETA receptors, supporting the role of the ET system in right ventricular hypertrophy.
Skip Nav Destination
Article navigation
December 2003
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 01 2003
Activation of the right ventricular endothelin (ET) system in the monocrotaline model of pulmonary hypertension: response to chronic ETA receptor blockade
Jean-François JASMIN;
Jean-François JASMIN
1Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8
Search for other works by this author on:
Peter CERNACEK;
Peter CERNACEK
1Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8
Search for other works by this author on:
Jocelyn DUPUIS
1Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8
Correspondence: Dr J. Dupuis (e-mail [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 16 2003
Revision Received:
June 23 2003
Accepted:
June 25 2003
Accepted Manuscript online:
June 25 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 105 (6): 647–653.
Article history
Received:
April 16 2003
Revision Received:
June 23 2003
Accepted:
June 25 2003
Accepted Manuscript online:
June 25 2003
Citation
Jean-François JASMIN, Peter CERNACEK, Jocelyn DUPUIS; Activation of the right ventricular endothelin (ET) system in the monocrotaline model of pulmonary hypertension: response to chronic ETA receptor blockade. Clin Sci (Lond) 1 December 2003; 105 (6): 647–653. doi: https://doi.org/10.1042/CS20030139
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |