(Circulation. 1995;92:1005-1010.)
© 1995 American Heart Association, Inc.
Articles |
Endogenous and Exogenous Nitric Oxide Protect Against Intracoronary Thrombosis and Reocclusion After Thrombolysis
From the Cullen Cardiovascular Research Laboratory at Texas Heart Institute and the Departments of Internal Medicine and Pathology and Laboratory Medicine at the University of Texas-Houston Medical School, Houston, Tex; and the Division of Cardiology (P.G.), Second School of Medicine, University of Naples, Italy.
Correspondence to James T. Willerson, MD, Department of Internal Medicine, University of Texas-Houston Medical School, PO Box 20708, Houston, TX 77225.
Background Nitric oxide (NO), an endothelium-derived relaxing factor, plays an important role in regulating platelet activation. We evaluated the effect of NO in a canine model of intracoronary thrombosis, thrombolysis, and reocclusion.
Methods and Results Before thrombosis was induced, 34 anesthetized dogs were treated with a continuous intracoronary infusion of saline (n=8); NG-nitro-L-arginine (L-NNA, n=8), an inhibitor of NO synthetase; L-arginine (n=7), the precursor for NO; or sodium nitroprusside (SNP, n=11), an NO donor. Ten minutes after the infusion was begun, an electric current of 150 µA was applied to the endothelium of coronary arteries to induce thrombosis. Occlusive thrombi developed in all dogs in the saline group (38±4 minutes) and the L-NNA group (30±6 minutes), in 6 of 7 dogs in the L-arginine group (81±18 minutes), and in 6 of 11 dogs in the SNP group (102±21 minutes) (P<.01). The time to thrombus was prolonged by L-arginine (P<.05) and SNP (P<.01). After 3 hours of thrombus formation in coronary arteries, tissue plasminogen activator and heparin were administered intravenously. Thrombi were lysed in 4 (of 8) dogs in the saline group (71±8 minutes), in 4 (of 8) dogs in the L-NNA group (72±8 minutes), in 4 (of 6) dogs in the L-arginine group (50±14 minutes), and in 4 (of 6) dogs in the SNP group (49±11 minutes) (P>.05). After thrombolysis, coronary artery reocclusion developed in all reperfused dogs in the saline group (30±8 minutes) and in the L-NNA group (48±12 minutes), in 3 (of 4) reperfused dogs in the L-arginine group (123±26 minutes), and in 3 (of 4) reperfused dogs in the SNP group (128±19 minutes) (P<.01). The ex vivo platelet aggregation induced by collagen was inhibited after in vivo treatment with L-arginine or SNP.
Conclusions Increasing NO production or giving an NO donor may inhibit platelet aggregation and delay intracoronary thrombus formation and reocclusion after thrombolysis.
Key Words: endothelium-derived relaxing factors • platelets • thrombolysis • thrombosis • occlusions
This article has been cited by other articles:
 |
|
 |
|
  G. Vilahur, E. Segales, E. Salas, and L. Badimon Effects of a Novel Platelet Nitric Oxide Donor (LA816), Aspirin, Clopidogrel, and Combined Therapy in Inhibiting Flow- and Lesion-Dependent Thrombosis in the Porcine Ex Vivo Model Circulation, September 21, 2004; 110(12): 1686 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakano, R. Tominaga, S. Morita, M. Masuda, I. Nagano, K.-i. Imasaka, and H. Yasui Impacts of pulsatile systemic circulation on endothelium-derived nitric oxide release in anesthetized dogs Ann. Thorac. Surg., July 1, 2001; 72(1): 156 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Bednar and C. E. Gross Antiplatelet Therapy in Acute Cerebral Ischemia Stroke, April 1, 1999; 30(4): 887 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Waugh, M. Kattash, J. Li, E. Yuksel, M. D. Kuo, M. Lussier, A. B. Weinfeld, R. Saxena, E. D. Rabinovsky, S. Thung, et al. Gene therapy to promote thromboresistance: Local overexpression of tissue plasminogen activator to prevent arterial thrombosis in an in vivo rabbit model PNAS, February 2, 1999; 96(3): 1065 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Bouchie, H. Hansen, and E. P. Feener Natriuretic Factors and Nitric Oxide Suppress Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells : Role of cGMP in the Regulation of the Plasminogen System Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1771 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Node, M. Kitakaze, H. Kosaka, T. Minamino, H. Mori, and M. Hori Role of Ca2+-Activated K+ Channels in the Protective Effect of ACE Inhibition Against Ischemic Myocardial Injury Hypertension, June 1, 1998; 31(6): 1290 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. W. Broeders, G.-J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G. A. oude Egbrink Endogenous Nitric Oxide Protects Against Thromboembolism in Venules But Not in Arterioles Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 139 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Nong, M. Hoylaerts, N. Van Pelt, D. Collen, and S. Janssens Nitric Oxide Inhalation Inhibits Platelet Aggregation and Platelet-Mediated Pulmonary Thrombosis in Rats Circ. Res., November 19, 1997; 81(5): 865 - 869. [Abstract] [Full Text]
|
|
|
|
|
|
K. Node, M. Kitakaze, H. Kosaka, T. Minamino, H. Funaya, and M. Hori Amelioration of Ischemia- and Reperfusion-Induced Myocardial Injury by 17ß-Estradiol : Role of Nitric Oxide and Calcium-Activated Potassium Channels Circulation, September 16, 1997; 96(6): 1953 - 1963. [Abstract] [Full Text]
|
|
|
|
|
|
M. Yamashita, R. A. Schmid, K. Ando, J. D. Cooper, and G. A. Patterson Nitroprusside Ameliorates Lung Allograft Reperfusion Injury Ann. Thorac. Surg., September 1, 1996; 62(3): 791 - 796. [Abstract] [Full Text]
|
|