INHIBITORY EFFECT OF CO ON INTERNAL ANAL-SPHINCTER - HEME OXYGENASE INHIBITOR INHIBITS NANC RELAXATION

We examined the effect and role of CO in opossum internal anal sphinct er (IAS) relaxation in response to nonadrenergic noncholinergic (NANC) nerve stimulation. Effects of NANC nerve stimulation on the IAS tensi on and second messengers (cAMP and cGMP) were examined before and afte r the selective heme oxygenase (HO) inhibitor zinc protoporphyrin IX ( Zn PP-IX). The HO activity of the IAS smooth muscle was determined bef ore and after NANC nerve stimulation. CO caused a concentration-depend ent and tetrodotoxin-resistant fall in the resting tension of the IAS. The direct action of CO was confirmed by its relaxant action on the i solated smooth muscle cells. Furthermore, CO caused an increase in the tissue cGMP levels comparable to that observed with nerve stimulation . Zn PP-IX caused suppression of IAS relaxation caused by NANC nerve s timulation and vasoactive intestinal polypeptide (VIP) but not by pept ide histidine-isoleucine and suppresssion of the increases in cGMP in response to NANC nerve stimulation. Zn PP-IX had no significant effect on the IAS responses to CO, nitric oxide (NO), and the beta-adrenocep tor agonist isoproterenol. The IAS responses to CO were not modified b y the NO synthase inhibitor NG-nitro-L-arginine. Significant HO activi ty was detected in the IAS, which increased further in response to NAN C nerve stimulation and VIP. The direct relaxant actions of CO and the suppression of NANC-mediated relaxation of the IAS by the HO inhibito r suggest the involvement of CO in the neurally mediated IAS relaxatio n.