Down-regulation of genes related to the adrenergic system may contribute to splanchnic vasodilation in rat portal hypertension.
OBJECTIVE
Splanchnic vasodilation initiates the hyperdynamic syndrome in portal hypertension. We aimed to explore molecular mechanisms involved in the development of mesenteric vasodilation in portal hypertension.


METHODS
Superior mesenteric artery (SMA) samples from portal vein ligated (PVL) and sham rats were compared in a time course experiment using DNA microarrays. Selected genes were quantified by qRT-PCR in PVL and cirrhotic rats. Inmunohistochemistry of tyrosine hydroxylase (Th) and norepinephrine was assessed in SMA sections of PVL and sham rats. Western blot analysis of Th, dopamine beta-hydroxylase (Dbh) and synaptosome-associated protein (Snap-25) was performed in SMA and jejunum samples from the animal models.


RESULTS
Fifty differentially expressed genes implicated in neurotransmission, especially adrenergic, were detected in SMA samples from PVL rats. Sequential analysis showed a profound down-regulation at 14 days in PVL rats. These down-regulated genes were confirmed by RT-PCR in SMA from PVL and cirrhotic rats. Th and NE detection by immunohistochemistry was reduced in PVL compared to sham. Th, Dbh and Snap-25 expression was lower in SMA from 14-day PVL and cirrhotic rats compared to sham and control rats, respectively.


CONCLUSIONS
Genetic down-regulation of genes related to the adrenergic system might have a role in splanchnic vasodilation of portal hypertension.
Coll
Mar
M
Liver Diseases Laboratory, Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-127, 08035 Barcelona, Spain.
Genescà
Joan
J
Raurell
Imma
I
Rodríguez-Vilarrupla
Aina
A
Mejías
Marc
M
Otero
Teresa
T
Oria
Marc
M
Esteban
Rafael
R
Guardia
Jaime
J
Bosch
Jaime
J
Martell
María
M
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D006975:Hypertension, Portal / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D007150:Immunohistochemistry; D008026:Ligation; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011169:Portal Vein; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013152:Splanchnic Circulation / Q000502:physiology*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
D012333:RNA, Messenger; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D002251:Carbon Tetrachloride; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine