Atrophy of mesenteric sympathetic innervation may contribute to splanchnic vasodilation in rat portal hypertension.
OBJECTIVE
Portal hypertension is associated with downregulation of mRNA and proteins involved in adrenergic transmission in the superior mesenteric artery (SMA) in portal vein-ligated (PVL) and cirrhotic rats. We aimed to investigate whether SMA adrenergic dysfunction was accompanied by sympathetic nerve structural changes and whether it was extensive to resistance mesenteric arteries. We also attempted to localize the origin of mRNA of specific adrenergic genes.


RESULTS
In situ hybridization showed tyrosine hydroxylase (Th) mRNA expression in neuronal bodies of superior mesenteric ganglia and inside axonal fibres surrounding proximal SMA sections. Comparison of SMA by Th immunohistochemistry, both in PVL and bile duct-ligated (BDL) rats, demonstrated a significant decrease in the number of nervous structures (69% PVL; 62% BDL), total nervous area (70% PVL; 52% BDL) and Th-stained nervous area (89% PVL; 64% BDL) compared with sham rats. A strong correlation was detected between the Th-stained nervous area and the haemodynamic parameters, mainly with SMA resistance (r=0.9, P<0.001 for PVL and r=0.75, P=0.018 for BDL). Western blot analysis of Th, dopamine beta-hydroxylase and synaptosome-associated protein of 25 kDa indicated a significant inhibition in protein expression (35-58%) in mesenteric resistance arteries from both portal hypertension models compared with sham. By contrast, nervous structure analysis and protein expression in renal arteries showed no differences between sham and PVL rats.


CONCLUSIONS
Portal hypertension is associated with sympathetic nerve atrophy/regression in the mesenteric arterial vasculature that could contribute to the splanchnic vasodilation associated with portal hypertension.
Coll
Mar
M
Liver Diseases Laboratory, Liver Unit, Department of Internal Medicine, Institut de Recerca Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Martell
María
M
Raurell
Imma
I
Ezkurdia
Nahia
N
Cuenca
Silvia
S
Hernández-Losa
Javier
J
Esteban
Rafael
R
Guardia
Jaume
J
Bosch
Jaume
J
Genescà
Joan
J
D000818:Animals; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D006439:Hemodynamics / Q000502:physiology; D006975:Hypertension, Portal / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000473:pathology*; D008643:Mesentery / Q000294:innervation* / Q000473:pathology; D009412:Nerve Fibers / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000235:genetics / Q000502:physiology*; D018709:Statistics, Nonparametric; D013564:Sympathetic Nervous System / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D012333:RNA, Messenger