Increased heme oxygenase activity in splanchnic organs from portal hypertensive rats: role in modulating mesenteric vascular reactivity

Background/Aims: We have recently demonstrated that heme oxygenase-1 is upr egulated in splanchnic organs of portal hypertensive rats. In the present s tudy, we assessed whether heme oxygenase enzymatic activity is increased in splanchnic organs of portal hypertensive rats, and the relative contributi on of heme oxygenase and nitric oxide synthase to the vascular hyporeactivi ty in portal hypertension. Methods: Heme oxygenase activity was measured in splanchnic organs of porta l hypertensive and sham-operated rats. The effects of heme oxygenase and ni tric oxide synthase inhibition on pressure responses to potassium chloride and methoxamine were assessed in perfused mesenteric vascular beds of porta l hypertensive and sham-operated rats. Results: Heme oxygenase activity was increased in the mesentery, intestine, liver, and spleen of portal hypertensive rats. The hyporeactivity to potas sium chloride in portal hypertensive rats was overcome after simultaneous i nhibition of both heme oxygenase and nitric oxide synthase, but only partia lly attenuated after nitric oxide synthase inhibition alone. The hyporeacti vity to methoxamine was completely reversed after nitric oxide synthase blo ckade. Conclusions: These results demonstrate that heme oxygenase activity is incr eased in splanchnic organs of portal hypertensive rats, They also suggest t hat heme oxygenase contributes to the hyporeactivity to potassium chloride, but not to methoxamine, in portal hypertensive rats. (C) 2001 European Ass ociation for the Study of the Liver. Published by Elsevier Science B,V, All rights reserved.