Cited by 1,633Nitric Oxide and Endothelin EffectsPhosphodiesterase function and regulationCardiovascular Health and Disease Prevention

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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

Ignarro, L J, Lippton, H, Edwards, J C, Baricos, W H, Hyman, A L, Kadowitz, P J, Gruetter, C A·1981·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(25)32738-2

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Thiol oxidation inhibits nitric oxide-mediated pulmonary artery relaxation and guanylate cyclase stimulation
Mingone, C. J., Gupte, S. A., Ali, N., et al. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00331.2005 · Cited by 31
“The early literature on the regulation of sGC has observations on how thiol oxidation can both enhance and inhibit basal cGMP production and sGC activation by agents thought to release NO (1, 3, 6, 14, 19, 22, 32, 35).”
BackgroundMethod
Nitroprusside, antihypertensive drug and analytical reagent
Leeuwenkamp, O. R., Bennekom, W. P. V., Mark, E. J. V. D., et al. (1984) · Pharmacy World & Science · doi:10.1007/bf01954040 · Cited by 31
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“Nitrovasodilators (organic nitrates and nitroprusside) exert their vasodilating e ects through the spontaneous or metabolic release of NO, or a closely related compound, from their molecule (Ignarro et al., 1981; Ignarro & Kadowitz, 1985; Murad, 1986; Feelisch, 1991).”
Background
Characterization of nitroglycerine-induced relaxation in human corpus cavernosum smooth muscle: implications to erectile physiology and dysfunction
Christ, G. J., Kim, D. C., Taub, H. C., Gondré, C. M., & Melman, A. (1995) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y95-735 · Cited by 29
Guanylate cyclase activation by organic nitrates in not mediated via nitrite
Romanin, C., & Kukovetz, W. R. (1988) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(88)80130-5 · Cited by 31
Nitroglycerin relaxes coronary artery of the pig with no change in glutathione content or glutathione S‐transferase activity
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Ginsenoside‐induced relaxation of human bronchial smooth muscle via release of nitric oxide
Tamaoki, J., Nakata, J., Kawatani, K., et al. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703511 · Cited by 30
“Brie¯y, using the nitrosothiol NO donor Snitroso-N-acetyl-DL-penicillamine (SNAP) as a standard (Ignarro et al., 1981), the relationship between the magnitude of electrical current and the concentration of SNAP in the medium was determined.”
Method
Thrombospondins: from structure to therapeutics
Roberts, D. D. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7483-2 · Cited by 32
Disulfide reductase systems in liver
Miller, C. G., & Schmidt, E. E. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14498 · Cited by 30
“NO was first recognized as a gaseous signalling molecule for its activities in vasodilation (Ignarro et al., 1981).”
Background
Nitric Oxide as a Communication Signal in Vascular and Neuronal Cells
Ignarro, L. J. (1996) · Elsevier eBooks · doi:10.1016/b978-012435555-2/50004-8 · Cited by 30
Self-citation
Effect of Inhaled Nitric Oxide on Normal Human Left Ventricular Function fn1fn1Dr. Hayward is a recipient of a Postgraduate Medical Research Scholarship from the National Health and Medical Research Council of Australia, Canberra, Australia. This work was supported by a Research Project Grant to Dr. Kelly from the National Heart Foundation of Australia, Canberra, Australia.
Hayward, C. S., Kalnins, W. V., Rogers, P. G., et al. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00143-5 · Cited by 30
Nitrate delivery systems in perspective
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Plasma arteriovenous cGMP difference as a useful indicator of nitrate tolerance in patients with heart failure.
Tsutamoto, T., Kinoshita, M., Ohbayashi, Y., et al. (1994) · Circulation · doi:10.1161/01.cir.90.2.823 · Cited by 30
Impaired endothelium-dependent relaxation in mesenteric arteries of reduced renal mass hypertensive rats
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Localized administration of sodium nitroprusside enhances its protection against platelet aggregation in stenosed and injured coronary arteries.
Willerson, J. T., Igo, S. R., Yao, S.-K., et al. (1996) · PubMed · Cited by 30
Altered peripheral vesodilator profile of nitroglycerin during long-term infusion of N-acetylcysteine
Boesgaard, S., Inversen, H. K., Wroblewski, H., et al. (1994) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)90515-0 · Cited by 30
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Sulfhydryl group donors potentiate the hypotensive effect of acetylcholine in rats.
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“Furthermore, sulfhydryl groups have been suggested as critical factors in the activation of guanylate cyclase by organic nitrates and NO through the formation of 5-nitrosothiols.(8) Studies of cultured endothelial cells using quantitative chemiluminescence techniques have reported that EDRF is more likely to be a nitr…”
Background
The Role of Nitric Oxide in Migraine Pain
Thomsen, L. L., Iversen, H. K., Lassen, L. H., et al. (1994) · CNS Drugs · doi:10.2165/00023210-199402060-00002 · Cited by 30
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Introduction and Overview
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Self-citation
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“…mechanical forces, including pulsatile or cyclic strain 15 and shear stress 16,17 ; third, by introducing exogenous compounds in the culture medium 18,19 or even affording a repertoire of growth factors stemming from the use of media conditioned by other cell types, 20,21 including ECs 22 ; and…”
Differentiation of L- and D-S-Nitrosothiol Recognition Sites In Vivo
Lewis, S. J., Hoque, A., & Bates, J. N. (2005) · Journal of Cardiovascular Pharmacology · doi:10.1097/01.fjc.0000181714.94827.5d · Cited by 29
“The differences in these responses may be related to the mechanisms by which these NO donors deliver NO to tissues or to additional mechanisms not necessarily related to NO delivery.(7,36,37) It was clear that the effects of NBT on the vasodilator actions of the test compounds were also not uniform.”
BackgroundInfluential
Emerging role of nitrite in myocardial protection
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“It has been proposed that low molecular weight thiols such as glutathione and cysteine, which react with nitric oxide or oxides of nitrogen to form nitrosothiols, are potential candidates for such a nitric oxide-carrier molecule (Ignarro et al., 1981).”
Background
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“NTG activates soluble guanylate cyclase, which results in increased cGMP production (9, 16, 22); NPs and NTG share a final common pathway through cGMP production.”
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Soluble guanylate cyclase
Hobbs, A. J. (2000) · Emerging Therapeutic Targets · doi:10.1517/14728222.4.6.735 · Cited by 29
Culture of rat mesenteric arteriolar smooth muscle cells: effects of platelet-derived growth factor, angiotensin, and nitric oxide on growth
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“SNAP, an experimental drug that releases nitric oxide (NO) spontaneously in aqueous medium (Ignarro et al. 1981), significantly (P < 0.”
Background
FR144420, a novel, slow, nitric oxide-releasing agent
Kita, Y., Ohkubo, K., Hirasawa, Y., et al. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)00750-2 · Cited by 29
A Pivotal Role of Nitric Oxide in Migraine Pain
Thomsen, L. L., & Olesen, J. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48642.x · Cited by 29
Interactions of Nitric Oxide and Redox-related species with biological targets
Maraj, S. R., Khan, S., Cui, X., Cammack, R., Joannou, C. L., & Hughes, M. (1995) · The Analyst · doi:10.1039/an9952000699 · Cited by 29
Endothelium‐derived relaxing factor (EDRF) and nitric oxide (NO). I. Physiology, pharmacology and pathophysiological implications
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Tokita, Y., Bessho, Y., Masu, M., Nakamura, K. D., Nakao, K., Katsuki, M., & Nakanishi, S. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01168.x · Cited by 30
“However, these unique receptors represent a minority of AMPA receptors (Iino et al., 1990).”
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In vitro studies of interactions of NO· donor drugs with superoxide and hydroxyl radicals
Dalloz, F., Maupoil, V., Lecour, S., Briot, F., & Rochette, L. (1997) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006821724773 · Cited by 29
“This complex inorganic salt which is rapidly inactivated in vivo [31], can spontaneously release NO· in neutral aqueous solutions [18, 28, 29, 30, 32], probably through a reductive mechanism of decomposition.”
Background
Effect of antioxidant treatments on nitrate tolerance development in normotensive and hypertensive rats
Cabassi, A., Bouchard, J., Dumont, É. C., Girouard, H., Jossec, M. L., Lamontagne, D., Besner, J., & de Champlain, J. (2000) · Journal of Hypertension · doi:10.1097/00004872-200018020-00009 · Cited by 29
Role of the endothelium in the response to cholinoceptor stimulation of rabbit ear and femoral arteries during cooling
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Determination of Nitrate and Nitrite Ions in Human Plasma by Ion Exchange-High Performance Liquid Chromatography
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Modification by LY 83583 and methylene blue of relaxation induced by nitric oxide, glyceryl trinitrate, sodium nitroprusside and atriopeptin in aortae of the rat, guinea-pig and rabbit
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Arterial Versus Venous Metabolism of Nitroglycerin to Nitric Oxide: A Possible Explanation of Organic Nitrate Venoselectivity
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Rapid tolerance to the hypotensive effects of glyceryl trinitrate in the rat: prevention by N‐acetyl‐ l ‐ but not N‐acetyl‐ d ‐cysteine
Newman, C. M., Warren, J. B., Taylor, G. W., Boobis, A. R., & Davies, D. S. (1990) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1990.tb13014.x · Cited by 27
Cholinesterase Inhibitor Blockade and its Prevention by Statins of Sympathetic α7-nAChR-Mediated Cerebral Nitrergic Neurogenic Vasodilation
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“Moreover, relaxation induced by sodium nitroprusside, which is known to release NO on entering the smooth muscle cells (Ignarro et al, 1981), was not affected by these three ChEIs either.”
Background
Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker
Wang, H., Qin, Y., Li, H., Roman, L. J., Pavel Martasek, E., Poulos, T. L., & Silverman, R. B. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00273 · Cited by 30
Methods for detection and characterization of protein S-nitrosylation
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Fluorophore-Labeled S-Nitrosothiols
Chen, X., Wen, Z., Xian, M., Wang, K., Ramachandran, N., Tang, X., Schlegel, H. B., Mutus, B., & Wang, P. G. (2001) · The Journal of Organic Chemistry · doi:10.1021/jo015658p · Cited by 28
Nitric Oxide Donors Stimulate Bile Flow and Glutathione Disulfide Excretion Independent of Guanosine 3′,5′–Cyclic Monophosphate in the Isolated Perfused Rat Liver
Trauner, M., Nathanson, M. H., Mennone, A., Rydberg, S. A., & Boyer, J. L. (1997) · Hepatology · doi:10.1002/hep.510250202 · Cited by 28
Relaxation Induced by Acetylcholine Involves Endothelium-Derived Hyperpolarizing Factor in 2-Kidney 1-Clip Hypertensive Rat Carotid Arteries
Oliveira, A. P. S., & Bendhack, L. M. (2004) · Pharmacology · doi:10.1159/000080378 · Cited by 28
N-Acetylcysteine Potentiates Nitroglycerin-Induced Reversal of Platelet Aggregation
Chirkov, Y. Y., & Horowitz, J. D. (1996) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199609000-00005 · Cited by 28
Inactivation of human aldehyde dehydrogenase by isosorbide dinitrate.
Mukerjee, N., & Pietruszko, R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31857-4 · Cited by 28
Developmental aspects of endothelial function.
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Involvement of Endogenous Noradrenaline Release in Methylene Blue-Induced Contraction of Isolated Rabbit Aorta
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Kinetics Studies of the Reaction of the Ruthenium Porphyrin Ru(OEP)(CO) with the S-Nitrosothiol N-Acetyl-1-amino-2-methylpropyl-2-thionitrite
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Differential mechanisms of urethral smooth muscle relaxation by several NO donors and nitric oxide
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Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat
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Mechanisms of nitrate action and vascular tolerance
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Effect of passive stretch on intracellular nitric oxide and superoxide activities in single skeletal muscle fibres: Influence of ageing
Palomero, J., Pye, D., Kabayo, T., & Jackson, M. J. (2011) · Free Radical Research · doi:10.3109/10715762.2011.637203 · Cited by 27
“Exposure of muscle cells to SNAP (250 μ M), a nitric oxide donor, was used as a positive control [32].”
Method
Pharmacological Preconditioning With Hyperbaric Oxygen: Can This Therapy Attenuate Myocardial Ischemic Reperfusion Injury and Induce Myocardial Protection via Nitric Oxide?
Yogaratnam, J. Z., Laden, G., Guvendik, L., Cowen, M., Cale, A. R. J., & Griffin, S. C. (2007) · Journal of Surgical Research · doi:10.1016/j.jss.2007.09.003 · Cited by 27
“While it can be appreciated that HBO2 is capable of producing NO [83] and that in the presence of superoxide, as may occur during treatment with HBO2 [94–96], NO may react with superoxide to produce peroxynitrite [61–64], which may go on to produce S-nitrosothiols that may also activate guanylate cyclase [78], how is…”
Background
Microwave-assisted hydrolysis of nitroglycerin (NG) under mild alkaline conditions: New insight into the degradation pathway
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“Nitric oxide has been described as an important degradation product inside mammalian cells and was identified of being responsible in the signaling mechanism in mammalian cells (Di Carlo, 1975; Ignarro et al., 1981; Ignarro, 2002; Kozlov et al., 2003).”
Background
Enhancing Cardiovascular Dynamics by Inhibition of Thrombospondin- 1/CD47 Signaling
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“These observations led to a search for the endothelial derived relaxing factor that controls smooth muscle contractility, which was found to be NO [14-17].”
Background
Inducible Nitric Oxide Synthase and Apoptosis in Murine Proximal Tubule Epithelial Cells
Tiwari, M., Messer, K. J., & Mayeux, P. R. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfj168 · Cited by 27
“These data support our in vivo findings in a murine model of LPS-induced ARF (Tiwari et al., 2005a) that suggest that iNOSinduced renal vascular dysfunction may play a more critical role in tubular injury and the development of LPS-induced ARF than direct tubular epithelium cytotoxicity.”
BackgroundMethodInfluential
Role of nitrates after acute myocardial infarction
Jugdutt, B. I. (1992) · The American Journal of Cardiology · doi:10.1016/0002-9149(92)90598-s · Cited by 27
Protective Effect of L-Arginine Intake on the Impaired Renal Vascular Responses in the Gentamicin-Treated Rats
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Long-Term Smoking Causes Nitroglycerin Resistance in Platelets by Depletion of Intraplatelet Glutathione
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THE RELATIONSHIP BETWEEN TISSUE LEVELS OF CYCLIC GMP AND TRACHEAL SMOOTH MUSCLE RELAXATION IN THE GUINEA‐PIG
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Endothelium-dependent relaxation resistant to NG-nitro-l-arginine in rat aorta
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Effects of Maturation on Cyclic GMP-Dependent Vasodilation in Ovine Basilar and Carotid Arteries
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The Role of Nitric Oxide in Glial Pathologya
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Nitrate tolerance
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How does nitroglycerin induce vascular smooth muscle relaxation?
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Blue light (λ=453 nm) nitric oxide dependently induces β-endorphin production of human skin keratinocytes in-vitro and increases systemic β-endorphin levels in humans in-vivo
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Background
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Self-citation
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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)
DOI: 10.1016/s0022-3565(25)32738-2
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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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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