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 noncholinergic nerve-mediated relaxation of gastrointestinal smooth muscle. Furthermore, hemoglobin is known to avidly bind NO and inhibit the nonadrenergic noncholinergic nerve-mediated smooth muscle relaxation. The influence of recombinant hemoglobin (rHb1.1) on gastrointestinal smooth muscle relaxation is not known. In this study, we examined the influence of rHb1.1 on the opossum internal anal sphincter (IAS) relaxation in response to electrical field stimulation, nitric oxide, vasoactive intestinal polypeptide, peptide histidine isoleucine and isoproterenol. The IAS smooth muscle strips developed spontaneous tone and exhibited frequency-dependent relaxation in response to electrical field stimulation. rHb1.1 caused concentration-dependent attenuation (30%-85%) of electrical field stimulation-induced IAS relaxation and complete obliteration of IAS relaxation induced by different concentrations of NO. rHb1.1 also caused suppression of the inhibitory effects of vasoactive intestinal polypeptide on IAS. Fall in the IAS tension by peptide histidine isoleucine and by isoproterenol were not modified by rHb1.1. The rHb1.1-induced blockade of neurally mediated IAS relaxations provides further support for the role of NO as an inhibitory neurotransmitter/mediator in the IAS.
Rattan
S
S
Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
Rosenthal
G J
GJ
Chakder
S
S
D001003:Anal Canal / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004558:Electric Stimulation; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D009893:Opossums; D010451:Peptide PHI / Q000494:pharmacology; D011994:Recombinant Proteins; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D006454:Hemoglobins; D010451:Peptide PHI; D011994:Recombinant Proteins; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D007545:Isoproterenol