Role of endothelium in the abnormal response of mesenteric vessels in rats with portal hypertension and liver cirrhosis.
OBJECTIVE
Previous studies have shown that nitric oxide synthesis inhibition corrects the hyporesponsiveness to vasoconstrictors present in the mesenteric vascular bed of portal-hypertensive rats. The origin of this elevated NO production, whether endothelial or muscular, is unknown. The aim of this study was to evaluate the role of vascular endothelium in the hyporesponsiveness to methoxamine (MTX) in the mesenteric vascular bed of portal vein-ligated (PVL) and cirrhotic rats.


METHODS
Endothelial denudation was achieved using a combined treatment of cholic acid and distilled water.


RESULTS
Compared with the respective control groups, PVL rats showed a reduced vascular response to MTX. Similar results were obtained in cirrhotic animals. The presence of ascites was associated with a more severe reduction in the response to MTX. Removal of the endothelium completely corrected the vascular hyporesponsiveness of PVL, cirrhotic nonascitic, and ascitic animals. In these experiments, acetylcholine-mediated vasodilation was practically absent whereas that of sodium nitroprusside was potentiated, which indicates a successful elimination of the endothelium and the preservation of smooth muscle function. Immunostaining for NO synthase isoforms revealed the presence of endothelial NO synthase protein in healthy and PVL rats exclusively in the endothelium.


CONCLUSIONS
The mesenteric vascular hyporesponsiveness to MTX present in these models of liver diseases and portal hypertension is solely due to endothelium-dependent factors.
Atucha
N M
NM
Hepatic Hemodynamic Laboratory, Veterans Affairs Medical Center, New Haven, Connecticut, USA.
Shah
V
V
García-Cardeña
G
G
Sessa
W E
WE
Groszmann
R J
RJ
D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D008729:Methoxamine