Circulation Research, Vol 61, 866-879, Copyright © 1987 by American Heart Association
ARTICLES |
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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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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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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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. [Abstract] [Full Text] |
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R. A. Cohen and P. M. Vanhoutte Endothelium-Dependent Hyperpolarization : Beyond Nitric Oxide and Cyclic GMP Circulation, December 1, 1995; 92(11): 3337 - 3349. [Full Text] |
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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. [Abstract] [Full Text] |
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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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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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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. 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] |
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