N‐substituted analogues of S‐nitroso‐N‐acetyl‐D,L‐penicillamine: chemical stability and prolonged nitric oxide mediated vasodilatation in isolated rat femoral arteries
Open accessAbstract
Previous studies show that linking acetylated glucosamine to S‐nitroso‐N‐acetyl‐D,L‐penicillamine (SNAP) stabilizes the molecule and causes it to elicit unusually prolonged vasodilator effects in endothelium‐denuded, isolated rat femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side‐chain), valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N‐substituted analogues of SNAP (2C), to further investigate other molecular characteristics that might influence chemical stability and duration of vascular action of S‐nitrosothiols. Spectrophotometric analysis revealed that SNVP was the most stable analogue in solution. Decomposition of all four compounds was accelerated by Cu(II) and cysteine, and neocuproine, a specific Cu(I) chelator, slowed decomposition of SNHP. Generation of NO from the compounds was confirmed by electrochemical detection at 37°C. Bolus injections of SNAP (10 μl; 10−8–10−3 M) into the perfusate of precontracted, isolated rat femoral arteries taken from adult male Wistar rats (400–500 g), caused concentration‐dependent, transient vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations induced by SNVP and SNHP were transient in endothelium‐intact vessels but failed to recover to pre‐injection pressures at moderate and high concentrations (10−6–10−3 M) in those denuded of endothelium. This sustained effect (>1 h) was most prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. We suggest that increased lipophilicity of SNAP analogues with longer sidechains facilitates their retention by endothelium‐denuded vessels; subsequent slow decomposition within the tissue generates sufficient NO to cause prolonged vasodilatation. This is a potentially useful characteristic for targeting NO delivery to areas of endothelial damage. British Journal of Pharmacology (1999) 126, 639–648; doi:10.1038/sj.bjp.0702346
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Lipophilic SNAP analogs with bulky side-chains prevent Cu+ catalysis through steric hindrance.
“Lipophilic analogs of SNAP (such as N-substituted derivatives of SNAPs) have also been developed by addition of bulky side-chains to N-acetylpenicillamine and preventing Cu+ catalysis through steric hindrance.187,188”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [187]
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Cites
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · see citing works
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,745 · see citing works
Garg, U. C., & Hassid, A. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114081 · Cited by 2,154 · see citing works
Role of endothelium-derived nitric oxide in the regulation of blood pressure.
Rees, D. D., Palmer, R. M. J., & Moncada, S. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.9.3375 · Cited by 1,827 · see citing works
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man
Vallance, P., Collier, J., & Moncada, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)91013-1 · Cited by 1,590 · see citing works
ENDOGENOUS NITRIC OXIDE INHIBITS HUMAN PLATELET ADHESION TO VASCULAR ENDOTHELIUM
Radomski, M. W., Palmer, R. M. J., & Moncada, S. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91481-4 · Cited by 1,437 · see citing works
Martin, W., Villani, G. M., Jothianandan, D., & Furchgott, R. F. (1985) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20898-9 · Cited by 1,259 · see citing works
An L-arginine/nitric oxide pathway present in human platelets regulates aggregation.
Radomski, M. W., Palmer, R. M., & Moncada, S. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.13.5193 · Cited by 1,208 · see citing works
The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium
Radomski, M. W., Palmer, R. M. J., & Moncada, S. (1987) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(87)80299-1 · Cited by 746 · see citing works
Palmer, R. M. J., & Moncada, S. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(89)80219-0 · Cited by 606 · see citing works
Endothelium-Dependent Hyperpolarization
Cohen, R. A., & Vanhoutte, P. M. (1995) · Circulation · doi:10.1161/01.cir.92.11.3337 · Cited by 518 · see citing works
Moncada, S., Rees, D. D., Schulz, R., & Palmer, R. M. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.6.2166 · Cited by 489 · see citing works
Aisaka, K., Gross, S. S., Griffith, O. W., & Levi, R. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92517-5 · Cited by 427 · see citing works
Förstermann, U., Mügge, A., Alheid, U., Haverich, A., & Frölich, J. C. (1988) · Circulation Research · doi:10.1161/01.res.62.2.185 · Cited by 418 · see citing works
Restoration of endothelium-dependent relaxation by dietary treatment of atherosclerosis.
Harrison, D. G., Armstrong, M. L., Freiman, P. C., & Heistad, D. D. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113276 · Cited by 352 · see citing works
Field, L., Dilts, R. V., Ravichandran, R., Lenhert, P. G., & Carnahan, G. E. (1978) · Journal of the Chemical Society Chemical Communications · doi:10.1039/c39780000249 · Cited by 290 · see citing works
Lipophilicity in drug action and toxicology
Pliška, V., Testa, B., & Waterbeemd, H. V. D. (1996) · Methods and principles in medicinal chemistry · doi:10.1002/9783527614998 · Cited by 267 · see citing works
Gardiner, S. M., Compton, A. M., Kemp, P. A., et al. (1990) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1990.tb14131.x · Cited by 266 · see citing works
Avdeef, A. (1993) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600820214 · Cited by 224 · see citing works
Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty
Ej, L., Brown, A. S., Belder, A. D., Smith, R. E. A., Martin, J., Wainwright, R. J., Thomas, M. R., Radomski, M. W., & Moncada, S. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90287-9 · Cited by 202 · see citing works
Chu, A. C., Chambers, D. E., Lin, C., Kuehl, W. D., Palmer, R. M. J., Moncada, S., & Cobb, F. R. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115223 · Cited by 198 · see citing works
Identification of Cu+ as the effective reagent in nitric oxide formation from S-nitrosothiols (RSNO)
Dicks, A. P., Swift, H. R., Williams, D. L. H., Butler, A. R., Al‐Sa'doni, H. H., & Cox, B. G. (1996) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/p29960000481 · Cited by 195 · see citing works
Self-citationPotentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine.
Horowitz, J. D., Antman, E. M., Lorell, B. H., Barry, W. H., & Smith, T. W. (1983) · Circulation · doi:10.1161/01.cir.68.6.1247 · Cited by 192 · see citing works
de Belder, A. J., MacAllister, R., Radomski, M. W., et al. (1994) · Cardiovascular Research · doi:10.1093/cvr/28.5.691 · Cited by 170 · see citing works
The possible role of copper ions in atherogenesis: the Blue Janus
Ferns, G. A., Lamb, D. J., & Taylor, A. (1997) · Atherosclerosis · doi:10.1016/s0021-9150(97)00130-5 · Cited by 143 · see citing works
S-Nitrosation and the reactions of S-nitroso compounds
Williams, D. L. H. (1985) · Chemical Society Reviews · doi:10.1039/cs9851400171 · Cited by 122 · see citing works
Flitney, F. W., Megson, I. L., Flitney, D. E., & BUTLER, A. R. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb14534.x · Cited by 110 · see citing works
Self-citationNitric Oxide: Nature's Naturally Occurring Leukocyte Inhibitor
Lefer, A. M. (1997) · Circulation · doi:10.1161/01.cir.95.3.553 · Cited by 108 · see citing works
Copper chelation‐induced reduction of the biological activity of S‐nitrosothiols
Gordge, M. P., Meyer, D. J., Hothersall, J. S., Neild, G. H., Payne, N. N., & Noronha-Dutra, A. A. (1995) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1995.tb13317.x · Cited by 105 · see citing works
Askew, S. C., Butler, A. R., Flitney, F. W., Kemp, G. D., & Megson, I. L. (1995) · Bioorganic & Medicinal Chemistry · doi:10.1016/0968-0896(94)00139-t · Cited by 93 · see citing works
Self-citationRole of a copper (I)‐dependent enzyme in the anti‐platelet action of S‐nitrosoglutathione
Gordge, M. P., Hothersall, J. S., Neild, G. H., & Noronha-Dutra, A. A. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15704.x · Cited by 91 · see citing works
Guerra, R., Brotherton, A. F., Goodwin, P. J., et al. (2008) · Blood Vessels · doi:10.1159/000158779 · Cited by 91 · see citing works
Effect of lipid feeding on endothelium dependent relaxation in rabbit aortic preparations
Chappell, S., Lewis, M., & Henderson, A. H. (1987) · Cardiovascular Research · doi:10.1093/cvr/21.1.34 · Cited by 88 · see citing works
Bauer, J. A., & Fung, H. L. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)23090-7 · Cited by 84 · see citing works
Comparative Evaluation of the Predictive Power of Calculation Procedures for Molecular Lipophilicity
Mannhold, R., Rekker, R. F., Sonntag, C., et al. (1995) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600841206 · Cited by 76 · see citing works
Caron, G., Gaillard, P., Carrupt, P., et al. (1997) · Helvetica Chimica Acta · doi:10.1002/hlca.19970800210 · Cited by 75 · see citing works
Self-citationAl‐Sa'doni, H. H., Megson, I. L., Bisland, S. K., BUTLER, A. R., & Flitney, F. W. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701218 · Cited by 70 · see citing works
Self-citationL-NMMA Increases blood pressure in man
Haynes, W. G., Noon, J. P., Walker, B. R., & Webb, D. J. (1993) · The Lancet · doi:10.1016/0140-6736(93)91981-q · Cited by 61 · see citing works
Self-citationMacAllister, R. J., Calver, A., Riezebos, J., Collier, J., & Vallance, P. J. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09496-0 · Cited by 60 · see citing works
Intramolecular Interactions Encoded in Lipophilicity: Their Nature and Significance
Testa, B., Carrupt, P., Gaillard, P., et al. (1996) · Methods and principles in medicinal chemistry · doi:10.1002/9783527614998.ch4 · Cited by 53 · see citing works
Assessment of Distribution‐pH Profiles
Avdeef, A. (1996) · Methods and principles in medicinal chemistry · doi:10.1002/9783527614998.ch7 · Cited by 53 · see citing works
Megson, I. L., Greig, I. R., Gray, G. A., et al. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701557 · Cited by 46 · see citing works
Self-citationKatsura, M., Ohkuma, S., Tsujimura, A., et al. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09685-5 · Cited by 45 · see citing works
Mechanisms of Liposomes/Water Partitioning of (p-Methylbenzyl)alkylamines
Fruttero, R., Caron, G., Fornatto, E., et al. (1998) · Pharmaceutical Research · doi:10.1023/a:1011953622052 · Cited by 39 · see citing works
Self-citationHongo, K., Ogawa, H., Kassell, N. F., et al. (1988) · Stroke · doi:10.1161/01.str.19.12.1550 · Cited by 36 · see citing works
Bainbrigge, N., Butler, A. R., & Görbitz, C. H. (1997) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/a604148e · Cited by 35 · see citing works
Self-citationMegson, I. L., Flitney, F. W., Bates, J., et al. (1995) · Endothelium · doi:10.3109/10623329509024657 · Cited by 32 · see citing works
Self-citationMan, J. G. D., Winter, B. Y. D., Boeckxstaens, G. E., Herman, A. G., & Pelckmans, P. A. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15769.x · Cited by 25 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- MONCADA, S., REES, D.D., SCHULZ, R. & PALMER, R.M.J. (1991). Development and mechanism of a speci®c supersensitivity to nitrovasodilators following inhibition of nitric oxide synthase in vivo. Proc. Natl. Acad. Sci. U.S.A., 88, 2166 ± 2170.
- SWIFT, H. (1989). PhD Thesis. Department of Chemistry, University of Durham, Durham, U.K.
- Pliska, V., Testa, B. & van de Waterbeemd, H. pp. 49 ± 71. Weinheim: VCH Publishers.
Cited by
Sorted by citations
Nitric oxide donors: chemical activities and biological applications
Wang, P. G., Xian, M., Tang, X., Wu, X., Wen, Z., Cai, T., & Janczuk, A. J. (2002) · Chemical Reviews · doi:10.1021/cr000040l · Cited by 1,337 · see citing works
Wo, Y., Brisbois, E. J., Bartlett, R. H., & Meyerhoff, M. E. (2016) · Biomaterials Science · doi:10.1039/c6bm00271d · Cited by 251 · see citing works
Wo, Y., Li, Z., Brisbois, E. J., Colletta, A., Wu, J., Major, T. C., Xi, C., Bartlett, R. H., Matzger, A. J., & Meyerhoff, M. E. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b07501 · Cited by 128 · see citing works
- Authors
- Megson, I. L., Morton, S., Greig, I. R., Mazzei, F. A., Field, R. A., Butler, A. R., Caron, G., Gasco, A., Fruttero, R., & Webb, D. J.
- Affiliations
- Western General Hospital (GB)
- University of St Andrews (GB)
- University of Turin (IT)
- Corresponding author
- Megson, I L
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1999-02
- Volume
- 126
- Issue
- 3
- Pages
- 639-648
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1565853
- OpenAlex
- W2013635851
- Cited by
- 49
- References
- 48
- Citations by year
- 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2017: 2 · 2016: 6 · 2015: 1 · 2014: 2 · 2013: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- S-nitrosothiols, nitric oxide, vasodilation, chemical stability, lipophilicity, side chain length, cysteine, femoral artery
- MeSH terms
- Animals, Endothelium, Vascular, Femoral Artery, Hydrogen-Ion Concentration, Male, Nitric Oxide, Penicillamine, Solubility, Vasodilation, Water, Rats, Wistar, 1-Octanol, Nitric Oxide Donors, Rats, In Vitro Techniques
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