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Cardiovascular Research 2006 69(3):764-771; doi:10.1016/j.cardiores.2005.08.021
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Copyright © 2005, European Society of Cardiology

Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure

Beatriz Somozaa, Fatima Abderrahima, José M. Gonzáleza, M. Victoria Condea, Silvia M. Arribasa, Barry Starchere, Javier Regaderab, María S. Fernández-Alfonsoc, Juan J. Díaz-Gild and M. Carmen Gonzáleza,*

aDepartamento de Fisiología, Facultad de Medicina, C/Arzobispo Morcillo 2, 28029 Madrid. Spain
bDepartamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma, Madrid, Spain
cInstituto Pluridisciplinar, Universidad Complutense, Madrid, Spain
dServicio de Bioquímica Experimental Hospital Puerta de Hierro, Madrid, Spain
eUniversity of Texas Health Center at Tyler, USA

* Corresponding author. Tel.: +34 914975475; fax: +34 914975353. Email address: m.c.gonzalez{at}uam.es

Objective: Liver growth factor (LGF), a mitogen for liver cells, reduces fibrosis in a rat model of cirrhosis. The present study assesses the possible vascular antifibrotic and antihypertensive effects of LGF treatment on spontaneously hypertensive rats (SHR).

Methods: Six-month-old male SHR and normotensive Wistar Kyoto rats (WKY) were treated with LGF (4.5 µg LGF/rat i.p. twice a week for 2 weeks). Haemodynamic parameters were measured in anaesthetized rats. Vascular structure and function were studied in carotid arteries using optical and confocal microscopy, radioimmunoassay for desmosine, and isometric tension recording.

Results: LGF reduced systolic and diastolic blood pressure only in SHR. When compared to those of untreated SHR, carotid arteries from LGF-treated SHR showed: 1) a 50% reduction in collagen area and an increase in vascular smooth muscle cell number in the media, 2) no difference in total elastin content, but an increase in size of fenestrae in the internal elastic lamina, and 3) enhanced relaxation to acetylcholine, sodium nitroprusside, and forskolin. These effects were specific for SHR, since no changes were observed in LGF-treated WKY.

Conclusion: Short-term treatment with a low dose of LGF induced a large improvement in vascular structure and function and significantly reduced blood pressure in a rat model of essential hypertension. The present results could open future research to explore the vascular effects of this endogenous factor in order to determine its potential as an antifibrotic and antihypertensive agent in humans.

KEYWORDS Arterial fibrosis; Liver growth factor; Hypertension; Vasodilatation; Extracellular matrix

Time for primary review 11 days


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