Vascular hyporesponsiveness in the mesenteric artery of anaesthetized rats with cirrhosis and portal hypertension: an in-vivo study.
BACKGROUND
Cirrhosis is complicated by splanchnic vasodilation. Nitric oxide (NO) and prostacyclin contribute to this. Vascular hyporesponsiveness has been reported, but the underlying pathophysiological mechanisms are unclear.


OBJECTIVE
This in-vivo study examined the contribution of NO and prostacyclin to the development of vascular hyporesponsiveness in the mesenteric circulation of animals with cirrhosis and portal hypertension.


METHODS
Rats underwent common bile duct ligation (CBDL) (n = 11), partial portal vein ligation (PPVL) (n = 12) and sham-operation (sham) (n = 11). Blood flow in the mesenteric artery (MBF) was measured during intramesenteric infusion of endothelium-dependent (acetylcholine) and endothelium-independent vasodilators (deta-NONOate, pinacidil) and a vasoconstrictor (L-phenylephrine). The measurements were repeated after systemic infusion of L-NAME (NO synthase inhibition) and indomethacin (cyclo-oxygenase inhibition).


RESULTS
The MBF response to acetylcholine was significantly lower in CBDL and tended to be lower in PPVL than in sham. L-NAME and indomethacin significantly decreased the MBF response to acetylcholine in all groups. The hyporeactivity to acetylcholine in CBDL and PPVL was maintained after L-NAME and indomethacin. The MBF response to pinacidil, deta-NONOate and phenylephrine, before and after NO synthase and cyclo-oxygenase inhibition, was lower in CBDL and PPVL than in sham.


CONCLUSIONS
This is the first in-vivo study demonstrating an impaired response to endothelium-dependent and endothelium-independent vasodilators as well as vasoconstrictors in the mesenteric artery of animals with cirrhosis and portal hypertension. The generalised hyporeactivity suggests an abnormality on the vascular smooth muscle cell level. The hyporesponsiveness persisted after combined NO synthase and cyclo-oxygenase inhibition.
Colle
Isabelle O
IO
Division of Hepato-Gastroenterology, Department of Medicine, Ghent University Hospital, Belgium. Isabelle.Colle@ugent.be
De Vriese
An S
AS
Van Vlierberghe
Hans R
HR
Lameire
Norbert H
NH
De Vos
Martine M
MM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006975:Hypertension, Portal / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase