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The FASEB Journal, Vol 9, 1319-1330, Copyright © 1995 by The Federation of American Societies for Experimental Biology

REVIEWS

Molecular mechanisms and therapeutic strategies related to nitric oxide

S Moncada and EA Higgs
Cruciform Project, London, United Kingdom.

The formation of nitric oxide (NO) from L-arginine is now recognized as a ubiquitous biochemical pathway involved in the regulation of the cardiovascular, central, and peripheral nervous systems, as well as in other homeostatic mechanisms. The L-arginine:NO pathway comprises a substrate, L-arginine, a family of enzymes, the NO synthases, and at least one physiological effector system, the soluble guanylate cyclase. NO also inhibits enzymes in target cells and can interact with oxygen- derived radicals to produce other toxic substances. Thus, NO also plays a role in immunological host defense and in the pathophysiology of certain clinical conditions. Several steps in the L-arginine:NO pathway are amenable to manipulation. Some substances will change the concentration and/or actions of NO with consequences that, in certain cases, may be therapeutic. In addition, other agents themselves generate NO and thus mimic the actions of the endogenous mediator. This brief overview will discuss some possible interventions in the pathway and the potential benefits as well as undesirable side effects that might arise from them.


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[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
N. Sennequier, D. Wolan, and D. J. Stuehr
Antifungal Imidazoles Block Assembly of Inducible NO Synthase into an Active Dimer
J. Biol. Chem., January 8, 1999; 274(2): 930 - 938.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
L. Moroz, R Gillette, and J. Sweedler
Single-cell analyses of nitrergic neurons in simple nervous systems
J. Exp. Biol., January 2, 1999; 202(4): 333 - 341.
[Abstract] [PDF]

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 J. Immunol.Home page
Y. Xiong, G. Karupiah, S. P. Hogan, P. S. Foster, and A. J. Ramsay
Inhibition of Allergic Airway Inflammation in Mice Lacking Nitric Oxide Synthase 2
J. Immunol., January 1, 1999; 162(1): 445 - 452.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
A. Friebe, F. Müllershausen, A. Smolenski, U. Walter, G. Schultz, and D. Koesling
YC-1 Potentiates Nitric Oxide- and Carbon Monoxide-Induced Cyclic GMP Effects in Human Platelets
Mol. Pharmacol., December 1, 1998; 54(6): 962 - 967.
[Abstract] [Full Text]

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 J. Pharmacol. Exp. Ther.Home page
G.-L. Liu, T. A. Christopher, B. L. Lopez, F. Gao, Y. Guo, E. Gao, K. Knuettel, M. Feelisch, and X. L. Ma
SP/W-5186, A Cysteine-Containing Nitric Oxide Donor, Attenuates Postischemic Myocardial Injury
J. Pharmacol. Exp. Ther., November 1, 1998; 287(2): 527 - 537.
[Abstract] [Full Text]

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 BloodHome page
O. Salvucci, J. P. Kolb, B. Dugas, N. Dugas, and S. Chouaib
The Induction of Nitric Oxide by Interleukin-12 and Tumor Necrosis Factor-alpha in Human Natural Killer Cells: Relationship With the Regulation of Lytic Activity
Blood, September 15, 1998; 92(6): 2093 - 2102.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
G. A. Sarosi, D. C. Barnhart, D. J. Turner, and M. W. Mulholland
Capacitative Ca2+ entry in enteric glia induced by thapsigargin and extracellular ATP
Am J Physiol Gastrointest Liver Physiol, September 1, 1998; 275(3): G550 - G555.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
K. Zhang and K. P. Patel
Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1998; 275(3): R728 - R734.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
K. Bhagat
Endothelial function and myocardial infarction
Cardiovasc Res, August 1, 1998; 39(2): 312 - 317.
[Full Text] [PDF]

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 JEMHome page
K. M. Kengatharan, S. De Kimpe, C. Robson, S. J. Foster, and C. Thiemermann
Mechanism of Gram-positive Shock: Identification of Peptidoglycan and Lipoteichoic Acid Moieties Essential in the Induction of Nitric Oxide Synthase, Shock, and Multiple Organ Failure
J. Exp. Med., July 20, 1998; 188(2): 305 - 315.
[Abstract] [Full Text] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
O. Kosonen, H. Kankaanranta, M. Lähde, P. Vuorinen, P. Ylitalo, and E. Moilanen
Nitric Oxide-Releasing Oxatriazole Derivatives Inhibit Human Lymphocyte Proliferation by a Cyclic GMP-Independent Mechanism
J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 215 - 220.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
Y. Liu, H. Christou, T. Morita, E. Laughner, G. L. Semenza, and S. Kourembanas
Carbon Monoxide and Nitric Oxide Suppress the Hypoxic Induction of Vascular Endothelial Growth Factor Gene via the 5' Enhancer
J. Biol. Chem., June 12, 1998; 273(24): 15257 - 15262.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. W. Vaughn, L. Kuo, and J. C. Liao
Estimation of nitric oxide production and reactionrates
Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H2163 - H2176.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
U. Bayraktutan, Z.-K. Yang, and A. M Shah
Selective dysregulation of nitric oxide synthase type 3 in cardiac myocytes but not coronary microvascular endothelial cells of spontaneously hypertensive rat
Cardiovasc Res, June 1, 1998; 38(3): 719 - 726.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
M. W. Vaughn, L. Kuo, and J. C. Liao
Effective diffusion distance of nitric oxide in the microcirculation
Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1705 - H1714.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
H. Li, S. A. Oehrlein, T. Wallerath, I. Ihrig-Biedert, P. Wohlfart, T. Ulshöfer, T. Jessen, T. Herget, U. Förstermann, and H. Kleinert
Activation of Protein Kinase Calpha and/or epsilon  Enhances Transcription of the Human Endothelial Nitric Oxide Synthase Gene
Mol. Pharmacol., April 1, 1998; 53(4): 630 - 637.
[Abstract] [Full Text]

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 Am. J. Physiol. Renal Physiol.Home page
N. D. Vaziri, Z. Ni, X. Q. Wang, F. Oveisi, and X. J. Zhou
Downregulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH
Am J Physiol Renal Physiol, April 1, 1998; 274(4): F642 - F649.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
P VALLANCE and I CHARLES
Nitric oxide as an antimicrobial agent: does NO always mean NO?
Gut, March 1, 1998; 42(3): 313 - 314.
[Full Text]

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 GutHome page
T D WARNER and S A McCARTNEY
NOS inhibitors in colitis: a suitable case for treatment?
Gut, February 1, 1998; 42(2): 152 - 153.
[Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
J. S. Luoma, P. Stralin, S. L. Marklund, T. P. Hiltunen, T. Sarkioja, and S. Yla-Herttuala
Expression of Extracellular SOD and iNOS in Macrophages and Smooth Muscle Cells in Human and Rabbit Atherosclerotic Lesions : Colocalization With Epitopes Characteristic of Oxidized LDL and Peroxynitrite-Modified Proteins
Arterioscler Thromb Vasc Biol, February 1, 1998; 18(2): 157 - 167.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
H. Kleinert, T. Wallerath, C. Euchenhofer, I. Ihrig-Biedert, H. Li, and U. Forstermann
Estrogens Increase Transcription of the Human Endothelial NO Synthase Gene : Analysis of the Transcription Factors Involved
Hypertension, February 1, 1998; 31(2): 582 - 588.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
Z.-q. Yan and G. K. Hansson
Overexpression of Inducible Nitric Oxide Synthase by Neointimal Smooth Muscle Cells
Circ. Res., January 23, 1998; 82(1): 21 - 29.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
F. M. FARACI and D. D. HEISTAD
Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels
Physiol Rev, January 1, 1998; 78(1): 53 - 97.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
A. Friebe and D. Koesling
Mechanism of YC-1-Induced Activation of Soluble Guanylyl Cyclase
Mol. Pharmacol., January 1, 1998; 53(1): 123 - 127.
[Abstract] [Full Text]

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 CirculationHome page
K. T. Weber
Extracellular Matrix Remodeling in Heart Failure : A Role for De Novo Angiotensin II Generation
Circulation, December 2, 1997; 96(11): 4065 - 4082.
[Full Text]

Home page
 CirculationHome page
Y. Fukumoto, H. Shimokawa, T. Kozai, T. Kadokami, K. Kuwata, Y. Yonemitsu, T. Kuga, K. Egashira, K. Sueishi, and A. Takeshita
Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1ß in Pigs in Vivo
Circulation, November 4, 1997; 96(9): 3104 - 3111.
[Abstract] [Full Text]

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 Cardiovasc ResHome page
M. Kelm, S. Schafer, R. Dahmann, B. Dolu, S. Perings, U. K.M Decking, J. Schrader, and B. E Strauer
Nitric oxide induced contractile dysfunction is related to a reduction in myocardial energy generation
Cardiovasc Res, November 1, 1997; 36(2): 184 - 194.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
I. J. Kullo, G. Mozes, R. S. Schwartz, P. Gloviczki, T. B. Crotty, D. A. Barber, Z. S. Katusic, and T. O'Brien
Adventitial Gene Transfer of Recombinant Endothelial Nitric Oxide Synthase to Rabbit Carotid Arteries Alters Vascular Reactivity
Circulation, October 7, 1997; 96(7): 2254 - 2261.
[Abstract] [Full Text]

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 J. Pharmacol. Exp. Ther.Home page
D. J. Wolff, D. S. Gauld, M. J. Neulander, and G. Southan
Inactivation of Nitric Oxide Synthase by Substituted Aminoguanidines and Aminoisothioureas
J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 265 - 273.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
C. Sciorati, P. Rovere, M. Ferrarini, S. Heltai, A. A. Manfredi, and E. Clementi
Autocrine Nitric Oxide Modulates CD95-induced Apoptosis in gamma delta T Lymphocytes
J. Biol. Chem., September 12, 1997; 272(37): 23211 - 23215.
[Abstract] [Full Text] [PDF]

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 BloodHome page
J. A. French II, D. Kenny, J. P. Scott, R. G. Hoffmann, J. D. Wood, A. G. Hudetz, and C. A. Hillery
Mechanisms of Stroke in Sickle Cell Disease: Sickle Erythrocytes Decrease Cerebral Blood Flow in Rats After Nitric Oxide Synthase Inhibition
Blood, June 15, 1997; 89(12): 4591 - 4599.
[Abstract] [Full Text] [PDF]

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 Pharmacol. Rev.Home page
S. Moncada, A. Higgs, and R. Furchgott
XIV. International Union of Pharmacology Nomenclature in Nitric Oxide Research
Pharmacol. Rev., June 1, 1997; 49(2): 137 - 142.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
H. Kankaanranta, R. G. Knowles, P. Vuorinen, O. Kosonen, P. Holm, and E. Moilanen
3-Morpholino-Sydnonimine-Induced Suppression of Human Neutrophil Degranulation is Not Mediated by Cyclic GMP, Nitric Oxide or Peroxynitrite: Inhibition of the Increase in Intracellular Free Calcium Concentration by N-Morpholino- iminoacetonitrile, a Metabolite of 3-Morpholino-Sydnonimine
Mol. Pharmacol., May 1, 1997; 51(5): 882 - 888.
[Abstract] [Full Text]


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