Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat
Open accessAbstract
It has been reported that mitochondrial aldehyde dehydrogenase (ALDH2) catalyzes the formation of glyceryl dinitrate and inorganic nitrite from glyceryl trinitrate (GTN), leading to an increase in cGMP and vasodilation in the coronary and systemic vascular beds. However, the role of nitric oxide (NO) formed from nitrite in mediating the response to GTN in the pulmonary vascular bed is uncertain. The purpose of the present study was to determine if nitrite plays a role in mediating vasodilator responses to GTN. In this study, intravenous injections of GTN and sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure under baseline and elevated tone conditions and decreases in systemic arterial pressure in response to GTN and sodium nitrite were attenuated by cyanamide, an ALDH2 inhibitor, whereas responses to the NO donor, sodium nitroprusside (SNP), were not altered. The decreases in pulmonary and systemic arterial pressure in response to GTN and SNP were not altered by allopurinol, an inhibitor of xanthine oxidoreductase, whereas responses to sodium nitrite were attenuated. GTN was ∼1,000-fold more potent than sodium nitrite in decreasing pulmonary and systemic arterial pressures. These results suggest that ALDH2 plays an important role in the bioactivation of GTN and nitrite in the pulmonary and systemic vascular beds and that the reduction of nitrite to vasoactive NO does not play an important role in mediating vasodilator responses to GTN in the intact chest rat.
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Numerous other nitrite reduction mechanisms have been identified including aldehyde dehydrogenase, carbonic anhydrase, and endothelial nitric oxide synthase.
“Numerous other nitrite reduction mechanisms have been identified besides those discussed above including: aldehyde dehydrogenase, carbonic anhydrase, and endothelial nitric oxide synthase [130–132].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [131]
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Cites
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807 · see citing works
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“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-citationCytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674 · cited 1× · see citing works
“Recent studies provide support for the hypothesis that the nitrite anion represents a storage form of NO that can have therapeutic effects (12, 15, 19, 27).”
BackgroundFurchgott, R. F., & Bhadrakom, S. (1953) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)05163-8 · Cited by 655 · cited 2× · see citing works
“The ability of sodium nitrite to relax isolated arteries was first reported by Furchgott and Bhadrakom (18) in 1953, and the effect of nitrite on soluble guanylyl cyclase activity and cGMP levels was documented by Ignarro et al.”
BackgroundDejam, A., Hunter, C. J., Tremonti, C., Pluta, R. M., Hon, Y. Y., Grimes, G., Partovi, K., Pelletier, M. M., Oldfield, E. H., Cannon, R. O., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.712133 · Cited by 334 · see citing works
Cardioprotective effects of acidified sodium nitrite in myocardial ischemia with reperfusion
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“The mechanism by which nitrite is reduced to NO in the rat is uncertain, but the reduction of inorganic nitrite to NO can be mediated by enzymatic mechanisms and by nonenzymatic disproportionation at low pH (12, 13, 16, 19, 22, 27, 35).”
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Lidder, S., & Webb, A. J. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04420.x · Cited by 360 · see citing works
Nitric oxide, a protective molecule in the cardiovascular system
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Inorganic nitrite therapy: historical perspective and future directions
Kevil, C. G., Kolluru, G. K., Pattillo, C. B., & Giordano, T. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.042 · Cited by 113 · see citing works
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Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension
Pankey, E. A., Badejo, A. M., Casey, D. B., Lasker, G. F., Riehl, R. A., Murthy, S. N., Nossaman, B. D., & Kadowitz, P. J. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.02.004 · Cited by 35 · see citing works
- Authors
- 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.
- Affiliations
- Tulane University (US)
- Department of Pharmacology, Tulane University School of Medicine, New Orleans; and
- Corresponding author
- Kadowitz, Philip J.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2010-09
- Volume
- 299
- Issue
- 3
- Pages
- H819-H826
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC2944483
- OpenAlex
- W2074007285
- Cited by
- 32
- References
- 6
- Citations by year
- 2023: 1 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-62000, HL-77421, R01HL077421, R01HL062000)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- mitochondrial aldehyde dehydrogenase, ALDH2, nitroglycerin, sodium nitrite, nitric oxide, pulmonary vasodilation, nitrite reduction, cyanamide, xanthine oxidoreductase, allopurinol, nitric oxide donors, pulmonary artery pressure, systemic blood pressure, cardiac output
- MeSH terms
- Aldehyde Dehydrogenase, Mitochondrial, Aldehyde Dehydrogenase, Analysis of Variance, Animals, Cyanamide, Enzyme Inhibitors, Nitroglycerin, Lung, Male, Mitochondria, Nitric Oxide, Pulmonary Circulation, Sodium Nitrite, Vasodilation, Vasodilator Agents, Rats, Sprague-Dawley, NG-Nitroarginine Methyl Ester, Mitochondrial Proteins, Rats
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