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


CONCLUSIONS
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.
Somoza
Beatriz
B
Departamento de Fisiología, Facultad de Medicina, C/Arzobispo Morcillo 2, 28029 Madrid, Spain.
Abderrahim
Fatima
F
González
José M
JM
Conde
M Victoria
MV
Arribas
Silvia M
SM
Starcher
Barry
B
Regadera
Javier
J
Fernández-Alfonso
María S
MS
Díaz-Gil
Juan J
JJ
González
M Carmen
MC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D005576:Colforsin / Q000494:pharmacology; D003094:Collagen / Q000032:analysis; D003895:Desmosine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000032:analysis; D005355:Fibrosis; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D018613:Microscopy, Confocal; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D008934:Mitogens; D012709:Serum Albumin; D014665:Vasodilator Agents; C053498:albumin-bilirubin complex; D003895:Desmosine; D009599:Nitroprusside; D005576:Colforsin; D003094:Collagen; D004549:Elastin; D000109:Acetylcholine; D001663:Bilirubin; D000075462:Serum Albumin, Human