Influence of heme oxygenase inhibitors on the basal tissue enzymatic activity and smooth muscle relaxation of internal anal sphincter

We examined the actions of different heme oxygenase (HO) inhibitors on the basal HO activity in the opossum internal anal sphincter (IAS), rectum, and liver tissues and the IAS smooth muscle relaxation in response to nonadren ergic noncholinergic (NANC) nerve stimulation and different agonists. All t he tissues examined were found to have significant levels of basal HO activ ity, Among different HO inhibitors, tin protoporphyrin IX (SnPP IX) was fou nd to be most selective in inhibiting the HO activity in the IAS smooth mus cle. Conversely, in the liver, all the HO inhibitors except SnPP IX caused significant inhibition of HO activity. Consistent with HO activity inhibiti on, the IAS smooth muscle relaxations caused by NANC nerve stimulation and vasoactive intestinal polypeptide also were inhibited by zinc protoporphyri n IX and SnPP IX. Zinc protoporphyrin IX also caused a significant attenuat ion of the IAS smooth muscle relaxation caused by isoproterenol. The IAS sm ooth muscle relaxation caused by nitric oxide was not significantly modifie d by any of the HO inhibitors. The data show the presence of HO activity in the IAS and other gastrointestinal tissues. The differential attenuation o f HO activity by different HO inhibitors in the IAS smooth muscle and liver confirms the presence of different isozymes of HO in different tissues. Su ppression of basal HO activity and the IAS smooth muscle relaxation induced by NANC nerve stimulation or VIP but not NO suggest that some of the stimu li that cause IAS smooth muscle relaxation may involve HO activity.