Acute and chronic cyclooxygenase blockage in portal-hypertensive rats: influence in nitric oxide biosynthesis.
OBJECTIVE
Prostacyclin and nitric oxide have been involved in the hyperkinetic syndrome in portal hypertension. The aim of this study was to investigate the relative contribution and possible interaction between prostacyclin and NO in this circulatory abnormality.


METHODS
Portal vein-ligated and sham-operated rats received indomethacin and vehicle either on a short-term (5 mg/kg subcutaneously) or long-term basis (5 mk.kg-1.day-1, continuous 7-day infusion with an osmotic minipump). Measurements of arterial pressure and superior mesenteric arterial flow (mL.min-1.kg-1, ultrasonic flow probe) were then performed before and after NG-nitro-L-arginine methyl ester (L-NAME) injection (13 mg/kg intravenously).


RESULTS
Short-term or long-term indomethacin treatment had no effect in sham-operated rats but significantly decreased mesenteric arterial flow in portal-hypertensive rats. Mesenteric flow remained higher after long-term than after short-term indomethacin treatment (54.5 +/- 2 vs. 46.1 +/- 2; P = 0.01). This blunted response to long-term indomethacin treatment was associated with an enhanced response to L-NAME, shown by greater increments in arterial pressure (29% +/- 3%) and mesenteric arterial resistance (209 +/- 22%) in indomethacin-treated rats than in rats receiving vehicle (19% +/- 2% and 130% +/- 20%; P < 0.05).


CONCLUSIONS
Both prostacyclin and NO contributed to splanchnic hyperemia in portal-hypertensive rats. There was an enhanced release of NO after long-term prostacyclin inhibition, suggesting that both vasodilatory systems interact, promoting splanchnic hyperemia in portal hypertension.
Fernández
M
M
Hepatic Hemodynamic Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
García-Pagán
J C
JC
Casadevall
M
M
Mourelle
M I
MI
Piqué
J M
JM
Bosch
J
J
Rodés
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D006975:Hypertension, Portal / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin