TITLE

Physiology and pathophysiology of nitric oxide

AUTHOR(S)
Ignarro, Louis J.
PUB. DATE
June 1996
SOURCE
Kidney International;Jun1996 Supplement, Vol. 49, pS2
SOURCE TYPE
Academic Journal
DOC. TYPE
Table of Contents
ABSTRACT
Nitric oxide (NO) was discovered to be a potent vasodilator, inhibitor of platelet aggregation, and active species of nitroglycerin before the discovery of endothelium- derived relaxing factor (EDRF) in 1980. Subsequent studies revealed that EDRF is NO, and is synthesized by mammalian cells from L-arginine through a complex oxidation reaction catalyzed by the flavo-hemoprotein NO synthase (NOS). NOS catalyzes the NADPH- and oxygen-dependent oxygenation of L-arginine to NO plus L-citrulline in a reaction that requires at least six cofactors including NADPH, FAD, FMN, tetrahydrobiopterin, heme, and calmodulin. NO elicits its known physiological actions by activating cytosolic guanylate cyclase, which converts GTP to cyclic GMP. Endothelial NOS and neuronal NOS are constitutively present and activated by increases in intracellular calcium triggered by endogenous chemicals. NO then diffuses into nearby target cells to elevate cyclic GMP levels and thereby trigger cell function. NOS activity can also be regulated by a negative feedback mechanism involving NO itself. Much greater quantities of NO are produced pathophysiologically by a distinct form of NOS that can be induced in vascular endothelium, smooth muscle and macrophages by endotoxin and cytokines. This high-output production of NO is not regulated by calcium and is cytotoxic by mechanisms involving interaction with iron-containing proteins.
ACCESSION #
23778449

 

Related Articles

  • Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular system. Mergia, Evanthia; Friebe, Andreas; Dangel, Oliver; Russwurm, Michael; Koesling, Doris // Journal of Clinical Investigation;Jun2006, Vol. 116 Issue 6, p1731 

    In the vascular system, the receptor for the signaling molecule NO, guanylyl cyclase (GC), mediates smooth muscle relaxation and inhibition of platelet aggregation by increasing intracellular cyclic GMP (cGMP) concentration. The heterodimeric GC exists in 2 isoforms (α1-GC, α2-GC) with...

  • Homers regulate calcium entry and aggregation in human platelets: a role for Homers in the association between STIM1 and Orai1. JARDIN, Isaac; ALBARRÁN, Letizia; BERMEJO, Nuria; SALIDO, Ginés M.; ROSADO, Juan A. // Biochemical Journal;7/ 1/2012, Vol. 445 Issue 1, p29 

    Homer is a family of cytoplasmic adaptor proteins that play different roles in cell function, including the regulation of G-protein-coupled receptors. These proteins contain an Ena (Enabled)/VASP (vasodilator-stimulated phosphoprotein) homology 1 domain that binds to the PPXXF sequence motif,...

  • Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in children with congenital heart defects. Breuer, J.; Leube, G.; Mayer, P.; Gebhardt, S.; Sieverding, L.; Häberle, L.; Heinemann, M.; Apitz, J.; Häberle, L // European Journal of Pediatrics;1998, Vol. 157 Issue 3, p194 

    Unlabelled: Nitric oxide (NO) reduces platelet aggregation in vitro. However, repeated measurements of platelet aggregation in infants and small children are impossible due to the large blood samples required. Instead, the expression of different platelet receptors mediating...

  • Endothelial calcium-activated potassium channels as therapeutic targets to enhance availability of nitric oxide. Kerr, Paul M.; Tam, Raymond; Narang, Deepak; Potts, Kyle; McMillan, Dane; McMillan, Kale; Plane, Frances // Canadian Journal of Physiology & Pharmacology;Jun2012, Vol. 90 Issue 6, p739 

    The vascular endothelium plays a critical role in vascular health by controlling arterial diameter, regulating local cell growth, and protecting blood vessels from the deleterious consequences of platelet aggregation and activation of inflammatory responses. Circulating chemical mediators and...

  • Interaction Potential and Tolerability of the Coadministration of Cilostazol and Aspirin. Mallikaarjun, S.; Forbes, W.P.; Bramer, S.L. // Clinical Pharmacokinetics;1999 Supplement, Vol. 37 Issue 6, p87 

    Objective: This study evaluated the effects of repeated oral drug administration with cilostazol alone and with aspirin (acetylsalicylic acid) on platelet aggregation, coagulation and bleeding time as well as the cilostazol-aspirin pharmacokinetic interaction in healthy males. Design: This was a...

  • Cilostazol inhibits cytokine-induced nuclear factor-κB activation via AMP-activated protein kinase activation in vascular endothelial cells. Yoshiyuki Hattori; Kunihiro Suzuki; Atsuko Tomizawa; Noriko Hirama; Toshie Okayasu; Sachiko Hattori; Hiroko Satoh; Kazumi Akimoto; Kikuo Kasai // Cardiovascular Research;Jan2009, Vol. 81 Issue 1, p133 

    Aims Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cyclic AMP (cAMP) levels and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. We hypothesized that cilostazol may prevent inflammatory cytokine...

  • Platelet-derived NO slows thrombus growth on a collagen type III surface. Williams, Robert H.; Nollert, Matthias U. // Thrombosis Journal;2004, Vol. 2, p11 

    Nitric oxide (NO) is a free radical that plays an important role in modulating platelet adhesion and aggregation. Platelets are a source of vascular NO, but since erythrocytes avidly scavenge NO, the functional significance of platelet-derived NO is not clear. Our purpose was to determine if NO...

  • Nitric Oxide and Oral Diseases: Can We Talk About It? De Sá Siqueira, Mariana Alves; Fischer, Ricardo Guimarães; Da Silva Figueredo, Carlos Marcelo; Brunini, Tatiana M. C.; Mendes-Ribeiro, Antônio C. // Cardiovascular & Hematological Agents in Medicinal Chemistry;2010, Vol. 8 Issue 2, p104 

    Nitric oxide (NO) is a short-lived intercellular messenger with multiple biological implications, such as regulation of blood pressure, inhibition of platelet adhesion and aggregation, bacterial-challenge and cytokine stimulation, and regulation of mineralized tissue function. NO synthase (NOS)...

  • Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery. Quinn, S; O'Brien, C; McLoughlin, P // Eye;Jul2003, Vol. 17 Issue 5, p628 

    Purpose: Vascular endothelial cell dysfunction has been noted in patients with normal pressure glaucoma. Although nitric oxide (NO) accounts for a large proportion of vasorelaxation in the posterior ciliary artery, considerable relaxation remains unexplained. We investigated the...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics