Vol. 283, Issue 3, G587-G594, September 2002
Endothelial COX-1 and -2 differentially affect
reactivity of MVB in portal hypertensive rats
M. A.
Potenza1,
O. A.
Botrugno1,
M.
A.
De Salvia1,
G.
Lerro1,
C.
Nacci1,
F. L.
Marasciulo1,
R.
Andriantsitohaina2, and
D.
Mitolo-Chieppa1
1 Section of Pharmacology, Department of
Pharmacology and Human Physiology, Medical School, University of
Bari, 70124 Bari, Italy; and 2 Faculté de
Pharmacie, Laboratoire de Pharmacologie et Physicochimie des
Interactions Cellulaires et Moléculaires, Unité Mixte de
Recherche Centre National de la Recherche Scientifique, 67401 Illkirch
Cedex, France
Expression of constitutive and inducible
cyclooxygenase (COX-1 and COX-2, respectively) and the role of
prostanoids were investigated in the aorta and mesenteric vascular bed
(MVB) from the portal vein-ligated rat (PVL) as a model of portal
hypertension. Functional experiments were carried out in MVB from PVL
and sham-operated rats in the absence or presence of the nonselective
COX inhibitor indomethacin or the selective inhibitors of COX-1
(SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins
were evaluated in aorta and MVB, and PGI2 production by
enzyme immunoassay of 6-keto-PGF1
was evaluated in the
aorta. In the presence of functional endothelium, decreased contraction
to norepinephrine (NE) and increased vasodilatation to ACh were
observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or
NS-398 reversed the hyporeactivity to NE and the increased endothelial
vasodilatation to ACh in PVL, with NS-398 being more potent than the
other two inhibitors. Upregulation of COX-1 and COX-2 expressions was
detected in aorta and MVB from PVL portal hypertensive rats, and
increased production of 6-keto-PGF1 was observed in
aorta from portal hypertensive rats. These results suggest that
generation of endothelial vasodilator prostanoids, from COX-1 and COX-2
isoforms, accounts for the increased mesenteric blood flow in portal hypertension.
vasodilator prostanoids; vascular hyporeactivity; resistance
vessels; cyclooxygenase; mesenteric vascular bed; portal vein-ligated
