Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Henriques-Coelho, T (Author) FMUP; Correia-Pinto, J (Author) Other; Roncon-Albuquerque R, Jr. (Author) Other; Baptista, MJ (Author) Other; Lourenço, AP (Author) FMUP; Oliveira, SM (Author) Other; Brandão-Nogueira, A (Author) Other; Teles, A (Author) Other; Fortunato, JM (Author) Other; Leite-Moreira, AF (Author) FMUP

Journal

Title: American Journal of Physiology - Heart and Circulatory Physiology

Vol. 287 No. 6

Pages: H2885-H2890

ISSN: 0363-6135

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 55 Citations

ISI Web of Science

Scopus - 63 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences

Other information

Authenticus ID: P-000-7CJ

DOI: 10.1152/ajpheart.01122.2003

Abstract (EN): We investigated the endogenous production of ghrelin as well as cardiac and pulmonary vascular effects of its administration in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a subcutaneous injection of ghrelin (100 mug/kg bid for 2 wk) or saline. Four groups were analyzed: normal rats treated with ghrelin (n = 7), normal rats injected with saline (n = 7), MCT rats treated with ghrelin (n = 9), and MCT rats injected with saline (n = 9). At 22-25 days, right ( RV) and left ventricular (LV) pressures were measured, heart and lungs were weighted, and samples were collected for histological and molecular analysis. Endogenous production of ghrelin was almost abolished in normal rats treated with ghrelin. In MCT-treated animals, pulmonary expression of ghrelin was preserved, and RV myocardial expression was increased more than 20 times. In these animals, exogenous administration of ghrelin attenuated PH, RV hypertrophy, wall thickening of peripheral pulmonary arteries, and RV diastolic disturbances and ameliorated LV dysfunction, without affecting its endogenous production. In conclusion, decreased tissular expression of ghrelin in healthy animals but not in PH animals suggests a negative feedback in the former that is lost in the latter. A selective increase of ghrelin mRNA levels in the RV of animals with PH might indicate distinct regulation of its cardiac expression. Finally, ghrelin administration attenuated MCT-induced PH, pulmonary vascular remodeling, and RV hypertrophy, indicating that it may modulate PH.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6