Evidence against a role for inducible nitric oxide synthase in the hyperdynamic circulation of portal-hypertensive rats.
OBJECTIVE
Excessive nitric oxide biosynthesis caused by expression of inducible NO synthase has been implicated in the hyperdynamic circulation of portal hypertension. The aim of the study was to investigate whether inducible NO synthase is expressed in portal hypertension an accounts for the hyperdynamic circulation.


METHODS
In study 1, NO synthase activities were measured by the conversion of L-arginine to citrulline in tissues from portal-hypertensive, cirrhotic, and sham-operated rats and from normal rats pretreated with endotoxin and after long-term administration of dexamethasone, which inhibits the expression of inducible NO synthase. In study 2, systemic and splanchnic hemodynamics (radiolabeled microspheres) and gastric blood flow (hydrogen gas clearance and reflectance spectrophotometry) were measured in portal-hypertensive rats after long-term administration of dexamethasone (0.25 mg.kg-1.day-1) or vehicle.


RESULTS
In study 1, constitutive and inducible NO synthase activities in portal-hypertensive or cirrhotic rats were similar to those observed in sham-operated rats. The significant increase in the inducible activity observed after endotoxin injection was prevented when rats received long-term treatment with dexamethasone. In study 2, cardiac index, portal-pressure, portal venous inflow, and gastric blood flow were similar in dexamethasone-or vehicle-treated portal-hypertensive rats.


CONCLUSIONS
These results to not support a role for an increased expression of the inducible NO synthase in the hyperdynamic circulation of portal hypertension.
Fernández
M
M
Hepatic Hemodynamic Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
García-Pagán
J C
JC
Casadevall
M
M
Bernadich
C
C
Piera
C
C
Whittle
B J
BJ
Piqué
J M
JM
Bosch
J
J
Rodés
J
J
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000201:enzymology* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase; D017082:Portal Pressure / Q000187:drug effects; D011169:Portal Vein / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013270:Stomach / Q000098:blood supply
D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases