Biomaterial Database

Cyclic GMP relaxes the internal anal sphincter in Hirschsprung's disease. 1995

K J VanderWall, and J F Bealer, and N S Adzick, and M R Harrison

Department of Surgery, University of California-San Francisco 94143-0570, USA.

In Hirschsprung's disease (HD), the aganglionic colon and internal anal sphincter (IAS) fail to relax. Aganglionic colon of HD patients relaxes in response to exogenous nitric oxide (NO), whereas the IAS from HD patients does not relax. The authors hypothesized that the failure of IAS relaxation is caused by a local deficiency of cyclic guanosine monophosphate (cGMP), the final metabolite in NO-mediated smooth muscle relaxation. To test this hypothesis, the authors measured the isometric tension of smooth muscle strips taken from the IAS and aganglionic colon of patients with HD before and after exposure to cGMP and compared this with ganglionic colon and IAS from normal controls. In HD patients both the IAS and aganglionic colon relaxed in response to cGMP (P < .05). The amount of relaxation observed in both the aganglionic colon and IAS was comparable to that measured in the normal controls. The observation that exogenous cGMP relaxes the IAS, whereas exogenous NO does not, suggests that mechanisms for relaxation may be different than those in the aganglionic colon and may explain persistent IAS dysfunction after resection of aganglionic colon. The defect of the IAS in HD may be the inability of the NO/cGMP pathway to induce smooth muscle cell relaxation rather than a defect in the smooth muscle cell.

UI	MeSH Term	Description	Entries
D007537	Isometric Contraction	Muscular contractions characterized by increase in tension without change in length.	Contraction, Isometric,Contractions, Isometric,Isometric Contractions
D009126	Muscle Relaxation	That phase of a muscle twitch during which a muscle returns to a resting position.	Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010726	Phosphodiesterase Inhibitors	Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.	Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D003106	Colon	The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.	Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D005724	Ganglia	Clusters of multipolar neurons surrounded by a capsule of loosely organized CONNECTIVE TISSUE located outside the CENTRAL NERVOUS SYSTEM.
D006152	Cyclic GMP	Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)	Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006627	Hirschsprung Disease	Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.	Aganglionosis, Colonic,Colonic Aganglionosis,Megacolon, Congenital,Aganglionic Megacolon,Aganglionosis, Rectosigmoid Colon,Aganglionosis, Total Colonic,Congenital Intestinal Aganglionosis,Congenital Megacolon,Hirschsprung's Disease,Megacolon, Aganglionic,Rectosigmoid Aganglionosis,Total Colonic Aganglionosis,Aganglionosis, Rectosigmoid,Disease, Hirschsprung,Disease, Hirschsprung's,Hirschsprungs Disease,Rectosigmoid Colon Aganglionosis
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man