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* To whom correspondence should be addressed. E-mail: amoreira{at}med.up.pt.
We investigated 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 sc injection of MCT (60 mg/Kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a sc injection of ghrelin (100 µg/Kg, BID for 2 weeks) 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 weighted and samples collected for histologic 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, 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, suggests a negative feedback in the former that is lost in the latter. 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.
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