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Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates
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“Nitrite metabolism can be activated by hypoxia, low pH and reactions with metalloproteins[50–58].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [50]
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Penile Erection in the Primate: Induction with Nitric-Oxide Donors
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Exogenous nitric oxide induces protection during hemorrhagic shock
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Nitric Oxide Inhibits the Degradation of IRP2
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“macological properties (5, 12), clearly suggest that NO antag-”
BackgroundInfluentialBonaventura, D., Oliveira, F. D. S., Lunardi, C. N., et al. (2006) · Nitric Oxide · doi:10.1016/j.niox.2006.04.260 · Cited by 37
Oxidative alterations of cyclooxygenase during atherogenesis
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Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction Trial
Zakeri, R., Levine, J. A., Koepp, G. A., Borlaug, B. A., Chirinos, J. A., LeWinter, M. M., VanBuren, P., Dávila‐Román, V. G., Fuentes, L. D. L., Khazanie, P., et al. (2015) · Circulation Heart Failure · doi:10.1161/circheartfailure.114.001598 · Cited by 37
“Endothelial Effects of Nitrates Nitrate vasorelaxant responses are thought to be mediated by the formation of nitric oxide (NO) or a closely related entity.(26) NO activates soluble guanylyl cyclase in vascular smooth muscle, prompting the synthesis of the second messenger cyclic guanosine monophosphate (cGMP).”
Inhibitors of platelet signal transduction as anti-aggregatory drugs
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“S-nitroso compounds have been observed as intermediates during degradation of organic nitrates [38] and are formed spontaneously by S-ni t rosylat ion of proteins with NO [52] .”
BackgroundHoshida, S., Nishida, M., Yamashita, N., Igarashi, J., Hori, M., Kamada, T., Kuzuya, T., & Tada, M. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00538-2 · Cited by 37
Radiation sensitisation by nitric oxide releasing agents.
Mitchell, J. B., Cook, J. A., Krishna, M. C., DeGraff, W., Gamson, J., Fisher, J. M., Christodoulou, D., & Wink, D. A. (1996) · Europe PMC (PubMed Central) · Cited by 37
Relationship of Pharmacokinetic and Pharmacodynamic Properties of the Organic Nitrates
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“There is general agreement that nitrate enters into the cell and is cleaved to inorganic nitrite (N02-), and then to nitrous oxide (NO) [Ignarro et al. 1981; Kobayashi et al. 1980;”
BackgroundRelaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels
Medina, P., Segarra, G., Martínez-León, J., et al. (2000) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(00)01914-7 · Cited by 37
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Relaxation mechanisms induced by stimulation of nerves and by nitric oxide in sheep urethral muscle.
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Evidence Mounts That Nitrite Contributes to Hypoxic Vasodilation in the Human Circulation
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Biological activity of hemoprotein nitrosyl complexes
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Lifestyle Modification in Metabolic Syndrome and Associated Changes in Plasma Amino Acid Profiles
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The effect of nitroglycerin on forearm arterial distensibility.
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Potential Role of Type 5 Phosphodiesterase Inhibition in the Treatment of Congestive Heart Failure
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Neurohormonal activation during nitrate therapy: A possible mechanism for tolerance
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Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension
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Role of ergothioneine on S-nitrosoglutathione catabolism
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Kinetics of parasite cysteine proteinase inactivation by NO-donors
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Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves
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“After induction of active tone with 5-HT (30 mM), EFS was applied for 10-s trains at maximal frequency (40 Hz) and tissues were frozen after 15 s as described previously (12, 14, 18).”
BackgroundMethodSelf-citationReversal of nitroglycerin tolerance in vitro by the cGMP-phosphodiesterase inhibitor zaprinast
Pagani, E. D., VanAller, G. S., O’Connor, B., et al. (1993) · European Journal of Pharmacology · doi:10.1016/0014-2999(93)90373-p · Cited by 35
Christiansen, I. S., Iversen, H. K., & Olesen, J. (2000) · Cephalalgia · doi:10.1046/j.1468-2982.2000.00064.x · Cited by 35
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Nitrate therapy for myocardial ischemic syndromes: Current perspectives including tolerance
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A nanoparticle delivery vehicle for S-nitroso-N-acetyl cysteine: Sustained vascular response
Nacharaju, P., Tuckman-Vernon, C., Maier, K. E., Chouake, J. S., Friedman, A., Cabrales, P., & Friedman, J. M. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.06.003 · Cited by 35
“S-nitrosation of various proteins has been implicated in physiological processes, including vasodilation, antimicrobial activity and other NO mediated cellular functions [15; 39; 43; 47; 55; 72].”
BackgroundControl of Plasma Nitric Oxide Bioactivity by Perfluorocarbons
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Nitric oxide synthase inhibitors for the treatment of chronic tension-type headache
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“The free radical NO is a messenger molecule involved in various biological functions [15,16] including neurotransmission [17].”
BackgroundAutoregulation of 1,25-dihydroxyvitamin D synthesis in macrophage mitochondria by nitric oxide.
Adams, J. S., & Ren, S. Y. (1996) · Endocrinology · doi:10.1210/endo.137.10.8828516 · Cited by 34
Treatment of Chronic Anal Fissure by Application of l-Arginine Gel: A Phase II Study in 15 Patients
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“The resultant rise of cytosolic cyclic guanylic acid mediates smooth muscle relaxation.(24,25) There are three isoforms of NOS: neuronal NOS, mainly localized to neurons; endothelial NOS, mainly localized to endothelium; and NOS, induced during tissue injury and inflammation.”
BackgroundLau, D. T. W., Chan, E. K., & Benet, L. Z. (1992) · Pharmaceutical Research · doi:10.1023/a:1015867031004 · Cited by 34
Nitric oxide donors preferentially inhibit neuronally mediated rat gastric acid secretion
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Wood, K. S., & Ignarro, L. J. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61148-2 · Cited by 34
Self-citationOn-line measurement of nitric oxide release from organic nitrates in the intact coronary circulation
Schr�r, K., F�rster, S., & Woditsch, I. (1991) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00167225 · Cited by 34
cGMP-induced differentiation of the promyelocytic cell line HL-60.
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Effects of sulfhydryl reagents on nitroglycerin-induced relaxation of bovine coronary artery
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Self-citationActions of nitric oxide on the acute gastrointestinal damage induced by PAF in the rat
Boughton-Smith, N. K., Deakin, A. M., & Whittle, B. J. R. (1992) · Inflammation Research · doi:10.1007/bf01991015 · Cited by 34
“Furthermore, the nitrovasodilator, S-nitroso-N-acetyl-penicillamine (SNAP), which spontaneously generates NO [9], attenuates both LPS-induced intestinal damage and its enhancement by L-NMMA [10].”
BackgroundDing, H., Keller, K. C., Martinez, I. K. C., Geransar, R. M., Nieden, K. O. Z., Nishikawa, S. G., Rancourt, D. E., & Nieden, N. I. Z. (2012) · Journal of Cell Science · doi:10.1242/jcs.081703 · Cited by 34
“In addition, PTIO (2-phenyl4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide; 100 mM] was used as a nitric oxide scavenger, while SNAP (S-nitroso-N-acetyl-penicillamine; 100 mM), was used as an exogenous NO donor (Ignarro et al., 1981).”
MethodNitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy
Oliveira‐Paula, G. H., & Tanus-Santos, J. E. (2018) · Current Drug Targets · doi:10.2174/1389450119666180816120816 · Cited by 33
Nitrate Therapy for Heart Failure
Gupta, D., Georgiopoulou, V. V., Kalogeropoulos, A. P., Marti, C. N., Yancy, C. W., Gheorghiade, M., Fonarow, G. C., Konstam, M. A., & Butler, J. (2013) · JACC Heart Failure · doi:10.1016/j.jchf.2013.03.003 · Cited by 33
Vascular and Hemodynamic Differences between Organic Nitrates and Nitrites
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Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages
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Glutathione Conjugation as a Mechanism for the Transport of Reactive Metabolites
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“Although the evidence presented in this and in previous studies (Ignarro et al., 1981b) indicate the involvement of S-nitrosothiols as active intermediates in the bioactivation of organic nitrate esters, the exact mechanism by which NO is released from them has yet to be fully elucidated.”
Nitrate therapy in the elderly
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Transient Corneal Edema Induced by Nitric Oxide Synthase Inhibition
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The Role of Nitric Oxide in Vascular Biology and Pathobiology
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Modulation of the pharmacological actions of nitrovasodilators by methylene blue and pyocyanin
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1-Nitrosomelatonin is a spontaneous NO-releasing compound
Blanchard-Fillion, B., Servy, C., & Ducrocq, C. (2001) · Free Radical Research · doi:10.1080/10715760100301351 · Cited by 33
“[14] The effects of pH and Cu ÷ and /o r Cu a÷ were compared taking account of the structural homology of 1-nitrosomelatonin with nitrosothiols (RS-NO) among other NO-donors.”
BackgroundNitric oxide is involved in 5‐HT‐induced relaxations of the guinea‐pig colon ascendens in vitro
Briejer, M. R., Akkermans, L. M. A., Meulemans, A. L. G., et al. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb14519.x · Cited by 33
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Tolerance to nitroglycerin is caused by reduced guanylate cyclase activation
Romanin, C. (1989) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(89)91491-0 · Cited by 33
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Totzeck, M., Hendgen-Cotta, U. B., Kelm, M., & Rassaf, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105951 · Cited by 32
Emerging role of nitric oxide in cancer
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Badejo, A. M., Hodnette, C., Dhaliwal, J. S., Casey, D. B., Pankey, E., Murthy, S. N., Nossaman, B. D., Hyman, A. L., & Kadowitz, P. J. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00959.2009 · Cited by 32
“The nitrite anion that is formed from the reaction of GTN with ALDH2 can be reduced to vasoactive NO or a NO-like compound that activates soluble guanylyl cyclase (26, 37).”
BackgroundMethodResultInfluentialSelf-citationMehra, A., Shotan, A., Ostrzega, E., Hsueh, W. A., Vasquez-Johnson, J., & Elkayam, U. (1994) · Circulation · doi:10.1161/01.cir.89.6.2595 · Cited by 32
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“Dose–response curves were performed to the endothelium-independent vasodilator (NO donor) (Ignarro et al., 1981), nitroprusside, and to the endothelium- and NO-independent vasodilator, papaverine.”
MethodDecreased nitric oxide‐mediated natural killer cell activation in chronic fatigue syndrome
Ogawa, Nishiura, Yoshimura, Horikawa, Yoshida, Okajima, Matsumura, Ishikawa, F., Nakao, Tomiyama, Y., et al. (1998) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1998.00373.x · Cited by 32
Bayır, H., Kochanek, P. M., Liu, S., Arroyo, A., Osipov, A. N., Jiang, J., Wisniewski, S. R., Adelson, P. D., Graham, S. H., & Kagan, V. E. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000040399.30600.e3 · Cited by 31
“S-nitrosothiols can serve as intermediates in the activation of guanylate cyclase (Ignarro et al., 1981; Mellion et al., 1983; Keaney et al., 1993; Scharfstein et al., 1994).”
BackgroundCivelli, M., Giossi, M., Caruso, P. L., et al. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15487.x · Cited by 32
Kulick, D., Roth, A., McIntosh, N. A., Rahimtoola, S. H., & Elkayam, U. (1988) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(88)90471-8 · Cited by 32
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Nitroglycerin therapy in the management of pulmonary hypertensive disorders
Packer, M., Halperin, J. L., Brooks, K. M., et al. (1984) · The American Journal of Medicine · doi:10.1016/0002-9343(84)91046-5 · Cited by 32
Inhibition of Platelet Aggregation with Glyceryl Trinitrate and Xanthine Oxidoreductase
O’Byrne, S., Shirodaria, C. C., Millar, T. M., Stevens, C. R., Blake, D. R., & Benjamin, N. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35295-4 · Cited by 31
“NO binds to the ferroheme prosthetic group of soluble guanylate cyclase, with increased production of guanosine 3Ј,5Ј-cGMP, resulting in vascular smooth muscle relaxation and inhibition of platelet aggregation (Ignarro et al., 1981; Hibbs et al., 1990).”
White, C. R., Moellering, D. R., Patel, R. P., KIRK, M. C., Barnes, S., & Darley-Usmar, V. M. (1997) · Biochemical Journal · doi:10.1042/bj3280517 · Cited by 32
Nitrate Tolerance from a Biochemical Point of View
Axelsson, K. L., & Ahlner, J. (1987) · Drugs · doi:10.2165/00003495-198700334-00013 · Cited by 32
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Liu, T., Schroeder, H. J., Power, G. G., & Blood, A. B. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102327 · Cited by 31
The role of lipoic acid in prevention of nitroglycerin tolerance
Dudek, M., Bednarski, M., Bilska‐Wilkosz, A., et al. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.06.073 · Cited by 31
Metadata
- Authors
- Ignarro, L. J., Lippton, H., Edwards, J. C., Baricos, W. H., Hyman, A. L., Kadowitz, P. J., & Gruetter, C. A.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1981-09
- Volume
- 218
- Issue
- 3
- Pages
- 739-749
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1907994445
- Cited by
- 1,633
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 10 · 2022: 11 · 2021: 6 · 2020: 8 · 2019: 14 · 2018: 23 · 2017: 10 · 2016: 15 · 2015: 16 · 2014: 14 · 2013: 16 · 2012: 27
- FWCI
- 18.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- vasorelaxation, organic nitrates, nitrite, sodium nitroprusside, nitric oxide, S-nitrosothiols, guanylate cyclase activation, cyclic GMP, nitroglycerin, isosorbide dinitrate, PETN, amyl nitrite, sodium nitrite, sulfhydryl groups, coronary arteries
- MeSH terms
- Animals, Biotransformation, Cats, Cattle, Coronary Vessels, Enzyme Activation, Female, Ferricyanides, Guanylate Cyclase, Hemodynamics, Male, Nitrates, Nitric Oxide, Nitrites, Nitroprusside, Nitroso Compounds, Vasodilator Agents, In Vitro Techniques
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