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Circulation Research. 1987;61:866-879

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Circulation Research, Vol 61, 866-879, Copyright © 1987 by American Heart Association


ARTICLES

Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical

LJ Ignarro, RE Byrns, GM Buga and KS Wood
Department of Pharmacology, University of California Los Angeles, School of Medicine 90024.

The objective of this study was to elucidate the close similarity in properties between endothelium-derived relaxing factor (EDRF) and nitric oxide radical (NO). Whenever possible, a comparison was also made between arterial and venous EDRF. In vascular relaxation experiments, acetylcholine and bradykinin were used as endothelium- dependent relaxants of isolated rings of bovine intrapulmonary artery and vein, respectively, and NO was used to relax endothelium-denuded rings. Oxyhemoglobin produced virtually identical concentration- dependent inhibitory effects on both endothelium-dependent and NO- elicited relaxation. Oxyhemoglobin and oxymyoglobin lowered cyclic guanosine monophosphate (cGMP) levels, increased tone in unrubbed artery and vein, and abolished the marked accumulation of vascular cGMP caused both by endothelium-dependent relaxants and by NO. The marked inhibitory effects of oxyhemoglobin on arterial and venous relaxant responses and cGMP accumulation as well as its contractile effects were abolished or reversed by carbon monoxide. These observations indicate that EDRF and NO possess identical properties in their interactions with oxyhemoproteins. Both EDRF from artery and vein and NO activated purified soluble guanylate cyclase by heme-dependent mechanisms, thereby revealing an additional similarity in heme interactions. Spectrophotometric analysis disclosed that the characteristic shift in the Soret peak for hemoglobin produced by NO was also produced by an endothelium-derived factor released from washed aortic endothelial cells by acetylcholine or A23187. Pyrogallol, via the action of superoxide anion, markedly inhibited the spectral shifts, relaxant effects, and cGMP accumulating actions produced by both EDRF and NO. Superoxide dismutase enhanced the relaxant and cGMP accumulating effects of both EDRF and NO. Thus, EDRF and NO are inactivated by superoxide in a closely similar manner. We conclude, therefore, that EDRF from artery and vein is either NO or a chemically related radical species.


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E. Thorin, P. L. Huang, M. C. Fishman, and J. A. Bevan
Nitric Oxide Inhibits {alpha}2-Adrenoceptor–Mediated Endothelium-Dependent Vasodilation
Circ. Res., June 29, 1998; 82(12): 1323 - 1329.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
E. Galea, E. V. Golanov, D. L. Feinstein, K. A. Kobylarz, S. B. Glickstein, and D. J. Reis
Cerebellar stimulation reduces inducible nitric oxide synthase expression and protects brain from ischemia
Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H2035 - H2045.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
S. Fujita, D. L Roerig, Z. J Bosnjak, and D. F Stowe
Effects of vasodilators and perfusion pressure on coronary flow and simultaneous release of nitric oxide from guinea pig isolated hearts
Cardiovasc Res, June 1, 1998; 38(3): 655 - 667.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
F. Perticone, R. Ceravolo, R. Maio, G. Ventura, A. Zingone, N. Perrotti, and P. L. Mattioli
Angiotensin-Converting Enzyme Gene Polymorphism Is Associated With Endothelium-Dependent Vasodilation in Never Treated Hypertensive Patients
Hypertension, April 1, 1998; 31(4): 900 - 905.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
H. Fujii, K. Ichimori, K. Hoshiai, and H. Nakazawa
Nitric Oxide Inactivates NADPH Oxidase in Pig Neutrophils by Inhibiting Its Assembling Process
J. Biol. Chem., December 26, 1997; 272(52): 32773 - 32778.
[Abstract] [Full Text] [PDF]


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J. Pharmacol. Exp. Ther.Home page
R. Rahimian, I. Laher, G. Dube, and C. v. Breemen
Estrogen and Selective Estrogen Receptor Modulator LY117018 Enhance Release of Nitric Oxide in Rat Aorta
J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 116 - 122.
[Abstract] [Full Text]


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Am. J. Respir. Cell Mol. Bio.Home page
L. S. Feder, D. Stelts, R. W. Chapman, D. Manfra, Y. Crawley, H. Jones, M. Minnicozzi, X. Fernandez, T. Paster, R. W. Egan, et al.
Role of Nitric Oxide on Eosinophilic Lung Inflammation in Allergic Mice
Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 436 - 442.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
M. Ding, B. A.St. Pierre, J. F. Parkinson, P. Medberry, J. L. Wong, N. E. Rogers, L. J. Ignarro, and J. E. Merrill
Inducible Nitric-oxide Synthase and Nitric Oxide Production in Human Fetal Astrocytes and Microglia. A KINETIC ANALYSIS
J. Biol. Chem., April 25, 1997; 272(17): 11327 - 11335.
[Abstract] [Full Text] [PDF]


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J. Cell Sci.Home page
S Khan, M Kayahara, U Joashi, N. Mazarakis, C Sarraf, A. Edwards, M. Hughes, and H Mehmet
Differential induction of apoptosis in Swiss 3T3 cells by nitric oxide and the nitrosonium cation
J. Cell Sci., January 9, 1997; 110(18): 2315 - 2322.
[Abstract] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
J. Lee, D. C. Drinkwater Jr., H. Laks, A. Chong, A. Blitz, M. A. Chen, L. J. Ignarro, and P. Chang
PRESERVATION OF ENDOTHELIUM-DEPENDENT VASODILATION WITH LOW-POTASSIUM UNIVERSITY OF WISCONSIN SOLUTION
J. Thorac. Cardiovasc. Surg., July 1, 1996; 112(1): 103 - 110.
[Abstract] [Full Text]


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HypertensionHome page
P. F. Pratt, M. Rosolowsky, and W. B. Campbell
Mediators of Arachidonic Acid–Induced Relaxation of Bovine Coronary Artery
Hypertension, July 1, 1996; 28(1): 76 - 82.
[Abstract] [Full Text]


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HypertensionHome page
K. S.K. Chang, M. Z. Zhong, and R. F. Davis
Indigo Carmine Inhibits Endothelium-Dependent and -Independent Vasodilation
Hypertension, February 1, 1996; 27(2): 228 - 234.
[Abstract] [Full Text]


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HypertensionHome page
C.-J. Tseng, H.-Y. Liu, H.-C. Lin, L.-P. Ger, C.-S. Tung, and M.-H. Yen
Cardiovascular Effects of Nitric Oxide in the Brain Stem Nuclei of Rats
Hypertension, January 1, 1996; 27(1): 36 - 42.
[Abstract] [Full Text]


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CirculationHome page
P. S. Tsao, N. P. Lewis, S. Alpert, and J. P. Cooke
Exposure to Shear Stress Alters Endothelial Adhesiveness : Role of Nitric Oxide
Circulation, December 15, 1995; 92(12): 3513 - 3519.
[Abstract] [Full Text]


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HypertensionHome page
C. E. Garcia, C. M. Kilcoyne, C. Cardillo, R. O. Cannon III, A. A. Quyyumi, and J. A. Panza
Effect of Copper-Zinc Superoxide Dismutase on Endothelium-Dependent Vasodilation in Patients With Essential Hypertension
Hypertension, December 1, 1995; 26(6): 863 - 868.
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CirculationHome page
R. A. Cohen and P. M. Vanhoutte
Endothelium-Dependent Hyperpolarization : Beyond Nitric Oxide and Cyclic GMP
Circulation, December 1, 1995; 92(11): 3337 - 3349.
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HypertensionHome page
N. L. Weintraub, A. H. Stephenson, R. S. Sprague, L. McMurdo, and A. J. Lonigro
Relationship of Arachidonic Acid Release to Porcine Coronary Artery Relaxation
Hypertension, October 1, 1995; 26(4): 684 - 690.
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CirculationHome page
A. A. Quyyumi, N. Dakak, N. P. Andrews, D. M. Gilligan, J. A. Panza, and R. O. Cannon III
Contribution of Nitric Oxide to Metabolic Coronary Vasodilation in the Human Heart
Circulation, August 1, 1995; 92(3): 320 - 326.
[Abstract] [Full Text]


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HypertensionHome page
M. Rosselli, B. Imthurn, P. J. Keller, E. K. Jackson, and R. K. Dubey
Circulating Nitric Oxide (Nitrite/Nitrate) Levels in Postmenopausal Women Substituted With 17ß-Estradiol and Norethisterone Acetate : A Two-Year Follow-up Study
Hypertension, April 1, 1995; 25(4): 848 - 853.
[Abstract] [Full Text]


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CirculationHome page
J. A. Panza, C. E. Garcia, C. M. Kilcoyne, A. A. Quyyumi, and R. O. Cannon III
Impaired Endothelium-Dependent Vasodilation in Patients With Essential Hypertension : Evidence That Nitric Oxide Abnormality Is Not Localized to a Single Signal Transduction Pathway
Circulation, March 15, 1995; 91(6): 1732 - 1738.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
J. L. Zweier, P. Wang, and P. Kuppusamy
Direct Measurement of Nitric Oxide Generation in the Ischemic Heart Using Electron Paramagnetic Resonance Spectroscopy
J. Biol. Chem., January 6, 1995; 270(1): 304 - 307.
[Abstract] [Full Text] [PDF]