Ghrelin reverses molecular, structural and hemodynamic alterations of the right ventricle in pulmonary hypertension.
Ghrelin is an endogenous peptide that has a dual effect by activating specific receptors and by stimulating release of growth hormone. There is increasing evidence that ghrelin has a potent vasodilator effect. Recently, we demonstrated that exogenous administration of ghrelin modulates its endogenous levels and attenuates the majority of alterations induced by monocrotaline (MCT). In the present study, we evaluate the effects of chronic administration of ghrelin on hemodynamic and morphometric parameters of the right ventricle, as well as on myocardial levels of SERCA2a and endothelin-1. Adult Wistar rats were injected with MCT (60 mg/kg, sc) or just the vehicle (day 0). One week later, the animals treated with MCT were randomly divided into two groups and treated with ghrelin (100 microg/kg, bid, sc) or with a similar volume of vehicle. Between days 21-25 the animals were instrumented to record right ventricular (RV) pressures and samples were collected for morphological and molecular analysis. Ghrelin treatment attenuated the effects of MCT, namely: RV myocyte fiber diameter, pulmonary vascular remodeling (evaluated by % medial wall thickness of peripheral arteries), RV peak systolic pressure, RV end-diastolic pressure, time constant tau, and SERCA2a and endothelin-1 mRNA levels. Chronic ghrelin administration attenuates MCT-induced pulmonary hypertension, vascular remodeling and RV hypertrophy. These results suggest a potential therapeutic role for the ghrelin-growth hormone axis in pulmonary hypertension.
Henriques-Coelho
Tiago
T
Serviço de Fisiologia, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Roncon-Albuquerque Júnior
Roberto
R
Lourenço
André P
AP
Baptista
Maria J
MJ
Oliveira
Sílvia M
SM
Brandão-Nogueira
Ana
A
Correia-Pinto
Jorge
J
Leite-Moreira
Adelino F
AF
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000032:analysis; D019332:Endothelin-1 / Q000032:analysis; D054439:Ghrelin; D013006:Growth Hormone / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D036361:Peptide Hormones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018497:Ventricular Dysfunction, Right
D019332:Endothelin-1; D054439:Ghrelin; D036361:Peptide Hormones; D013006:Growth Hormone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases