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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“18 Moreover, a thiol intermediate has been strongly implicated in the action of nitrosovasodilators like nitroglycerin.(20) Nevertheless, the overwhelming impression given by article titles, texts, and the name used for the enzyme synthesizing a g cyclase-activating factor(37) is that EDRFACh is NO.”
Background
Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.
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Background
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“Here we show that SNAP, another NO donor (Ignarro et al., 1981; Southam and Garthwaite, 1991), produced similar effects.”
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Self-citation
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“The mechanism of GTN's vasodilator action is generally agreed to involve denitration and release of NO from GTN which in turn activates smooth muscle guanylyl cyclase, causing vasorelaxation (Ignarro et al., 1981; Murad, 1986; Salvemini et al., 1992).”
Background
Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response
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“(2008) 9(17) Discovery of NO as the endothelium-derived relaxing factor opened the door to a wide research arena [3,11,12].”
Background
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“Mechanism of nitric oxide release from S-nitrosothiols.”
BackgroundInfluential
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“NO-induced vasodilatation is mediated by activation of soluble guanylate cyclase (sGC), which converts guanosine triphosphate into cyclic guanosine monophosphate (cGMP), and subsequently relaxes vascular smooth muscle (Ignarro et al., 1981).”
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“Even the more structurally complex organic nitrate and nitrite esters were demonstrated to elicit vascular smoothmuscle relaxation by being metabolized to NO (Ignarro et al., 1981).”
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Fluorometric Detection of BiologicalS-Nitrosothiols
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Enhanced release of nitric oxide causes increased cytotoxicity of S-nitroso-N-acetyl- dl -penicillamine and sodium nitroprusside under hypoxic conditions
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“It is known that cGMP is the intracellular mediator of vasodilator responses to sodium nitroprusside, which spontaneously liberates NO, an activator of soluble guanylate cyclase.(18) cGMP is also a mediator of vasodilatory responses to”
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Nitro containing L-arginine analogs interfere with assays for nitrate and nitrite
Greenberg, S. S., Xie, J., Spitzer, J. J., Wang, J., Lancaster, J. R., Grisham, M. B., Powers, D. R., & Giles, T. D. (1995) · Life Sciences · doi:10.1016/0024-3205(95)02181-h · Cited by 58
Nitrate Tolerance
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Vascular endothelial cells and dysfunctions role of melatonin
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“The primary mechanism by which NO relaxes vascular smooth muscle is by increasing intracellular cyclic GMP levels, followed by activation of protein kinase G and the subsequent phosphorylation of several regulatory proteins (50, 51).”
Background
Chemiluminescence headspace-gas analysis for determination of nitric oxide formation in biological systems
Brien, J. F., McLaughlin, B. E., Nakatsu, K., & Marks, G. S. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)68011-2 · Cited by 56
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Tolerance to relaxation in rat aorta: comparison of an S-nitrpsothiol with nitroglycerin
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“Endothelial NO plays a critical role in the regulation of vascular homeostasis by inhibiting inflammatory cell function and smooth muscle proliferation [1,2].”
Background
Characterization of the hypotensive effect of S-nitroso-N-acetylcysteine in normotensive and hypertensive conscious rats
Ricardo, K. F. S., Shishido, S. M., de Oliveira, M. G., & Krieger, M. H. (2002) · Nitric Oxide · doi:10.1016/s1089-8603(02)00009-5 · Cited by 56
Nitric oxide stimulates tyrosine phosphorylation in murine fibroblasts in the absence and presence of epidermal growth factor
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Evidence for the involvement of cGMP in neural bronchodilator responses in humal trachea.
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Inhibition of glutamate-induced cell death by sodium nitroprusside is not mediated by nitric oxide
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Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans.
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Short and long-acting oral nitrates for stable angina pectoris
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“This process requires sulfhydryl groups [34]; NO or nitrosothiols stimulate soluble guanylate cyclase to produce cyclic guanosine monophosphate [37].”
Background
Alterations of the vascular and the myocardial guanylate cyclase/cGMP-system induced by long-term hypertension in rats
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“However, as mentioned earlier, nitrosothiols are suspected by some investigators [10-18] of being the transport form of NO.”
Background
NITRIC OXIDE IN ATHEROSCLEROSIS: VASCULAR PROTECTOR OR VILLAIN?
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“…of conditions such as angina and heart failure has been advocated for over a century (Brunton, 1867), although the mechanism of action of such compounds was not elucidated until the late 1970s and found to involve metabolic conversion to NO and subsequent activation of sGC (Ignarro et al., 1981).”
Background
Direct-Acting Vasodilators
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“to be related to generation of nitric oxide gas as a consequence of their metabolic breakdown.(15) The pattern of vascular effect appears to differ, however, depending on the drug and its concentration at the vascular site of action.”
Background
Nitroglycerin Fails to Lower Blood Pressure in Redox-Dead Cys42Ser PKG1α Knock-In Mouse
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Nitroglycerin and long-acting nitrates in clinical practice
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“lgnarro et al [5]”
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“There is evidence that RSNOs are potent vasodilators and inhibitors of platelet aggregation (Ignarro and Gruetter, 1980; Ignarro et al., 1981; Kelm and Schrader, 1990; Stamler et al., 1992b; Butler and Williams, 1993).”
Background

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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