HUMAN RECOMBINANT HEMOGLOBIN (RHB1.1) INHIBITS NONADRENERGIC NONCHOLINERGIC (NANC) NERVE-MEDIATED RELAXATION OF INTERNAL ANAL-SPHINCTER

Nitric oxide (NO) plays a significant role in the nonadrenergic noncho linergic nerve-mediated relaxation of gastrointestinal smooth muscle. Furthermore, hemoglobin is known to avidly bind NO and inhibit the non adrenergic noncholinergic nerve-mediated smooth muscle relaxation. The influence of recombinant hemoglobin (rHb1.1) on gastrointestinal smoo th muscle relaxation is not known. In this study, we examined the infl uence of rHb1.1 on the opossum internal anal sphincter (IAS) relaxatio n in response to electrical field stimulation, nitric oxide, vasoactiv e intestinal polypeptide, peptide histidine isoleucine and isoproteren ol. The IAS smooth muscle strips developed spontaneous tone and exhibi ted frequency-dependent relaxation in response to electrical field sti mulation. rHb1.1 caused concentration-dependent attenuation (30%-85%) of electrical field stimulation-induced IAS relaxation and complete ob literation of IAS relaxation induced by different concentrations of NO , rHb1.1 also caused suppression of the inhibitory effects of vasoacti ve intestinal polypeptide on IAS. Fall in the IAS tension by peptide h istidine isoleucine and by isoproterenol were not modified by rHb1.1. The rHb1.1-induced blockade of neurally mediated IAS relaxations provi des further support for the role of NO as an inhibitory neurotransmitt er/mediator in the IAS.