INCREASED BLOOD HEMOGLOBIN ATTENUATES SPLANCHNIC VASODILATION IN PORTAL-HYPERTENSIVE RATS BY NITRIC-OXIDE INACTIVATION

Background & Aims: 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 hemoglo bin concentration by erythropoietin treatment on the gastrointestinal vasodilatation associated with portal hypertension. Methods: Portal-hy pertensive and sham-operated rats treated with erythropoietin were stu died 2 weeks after surgery. Hemodynamic and rheological parameters wer e measured in baseline conditions and after N-G-nitro-L-arginine methy l 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 pa rameters 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 e rythropoietin administration and by a similar in vitro relaxation to a cetylcholine in mesenteric artery rings. In portal-hypertensive rats, erythropoietin blunted the blood pressure response to sodium nitroprus side and attenuated the gastric and mesenteric blood flow response to L-NAME. Conclusions: Gastrointestinal vasodilatation associated with p ortal hypertension can be attenuated by increasing blood hemoglobin co ncentration. Inactivation of overproduced NO by hemoglobin may account for this effect.