Increased blood hemoglobin attenuates splanchnic vasodilation in portal-hypertensive rats by nitric oxide inactivation.
OBJECTIVE
Nitric oxide, which is quenched by hemoglobin, has been implicated in the pathogenesis of portal hypertension. The aim of this study was to investigate the effects of increasing blood hemoglobin concentration by erythropoietin treatment on the gastrointestinal vasodilation associated with portal hypertension.


METHODS
Portal-hypertensive and sham-operated rats treated with erythropoietin were studied 2 weeks after surgery. Hemodynamic and rheological parameters were measured in baseline conditions and after N(G)-nitro-L-arginine methyl ester (L-NAME) or sodium nitroprusside treatment.


RESULTS
In portal-hypertensive rats, erythropoietin attenuated the increase in gastric mucosal and superior mesenteric artery blood flows and the decrease in arterial blood pressure and splanchnic vascular resistances. Those parameters were not affected by erythropoietin in sham-operated rats. A direct vascular effect of erythropoietin was ruled out by the lack of changes in blood pressure or mesenteric blood flow after intravenous erythropoietin administration and by a similar in vitro relaxation to acetylcholine in mesenteric artery rings. In portal-hypertensive rats, erythropoietin blunted the blood pressure response to sodium nitroprusside and attenuated the gastric and mesenteric blood flow response to L-NAME.


CONCLUSIONS
Gastrointestinal vasodilation associated with portal hypertension can be attenuated by increasing blood hemoglobin concentration. Inactivation of overproduced NO by hemoglobin may account for this effect.
Casadevall
M
M
Gastroenterology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Piqué
J M
JM
Cirera
I
I
Goldin
E
E
Elizalde
I
I
Panés
J
J
Martínez-Cuesta
M A
MA
Bosch
J
J
Terés
J
J
Rodés
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply; D006454:Hemoglobins / Q000378:metabolism*; D006975:Hypertension, Portal / Q000097:blood / Q000503:physiopathology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D014665:Vasodilator Agents; D004921:Erythropoietin; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester