© 1996 American Heart Association, Inc.
Articles |
Chronic Inhalation of Nitric Oxide Inhibits Neointimal Formation After Balloon-Induced Arterial Injury
From the Cardiovascular Research Center and Cardiac Unit of the General Medical Service and Department of Anaesthesia at Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Kenneth D. Bloch, MD, Cardiovascular Research Center, CNY-4, Massachusetts General Hospital, 149 13th St, Charlestown, MA 02129. E-mail blochk@helix.mgh.harvard.edu.
Abstract Systemic and local intravascular NO administration inhibits neointimal formation after vascular injury in animal models. NO appears to attenuate smooth muscle proliferation both directly and indirectly by preventing the release of growth factors. Inhalation of low concentrations of NO dilates pulmonary vascular smooth muscle but does not cause systemic vasodilatation. Recently, NO inhalation was found to inhibit platelet function in vivo. We studied the effects of NO inhalation on neointimal formation after balloon-induced injury of the adult rat carotid artery. Beginning 60 minutes before carotid injury, rats breathed either air with 0 or 80 ppm NO for 14 days. Rats were killed, carotid arteries were fixed and paraffin-embedded, and neointimal formation was measured by analyzing the ratio of intimal to medial areas (I/M ratio) in carotid artery cross sections. Intimal hyperplasia was evident in both groups of animals, but I/M ratios were 43% less in animals breathing 80 ppm NO for 2 weeks than in animals breathing air alone (0.78±0.12 and 1.37±0.11 [mean±SE], respectively; P<.02). Similarly, 1 week after carotid injury, neointimal formation was less in rats breathing 80 ppm NO than in rats breathing air alone (I/M ratio, 0.39±0.11 versus 0.76±0.06; P<.02). Breathing 20 ppm NO for 2 weeks or 80 ppm NO for 1 week followed by air alone for 1 week did not attenuate neointimal formation measured at 14 days. In anesthetized rats breathing 80 ppm NO or air alone for 1 hour, neither systemic blood pressure nor bleeding time differed. These observations demonstrate that inhaling 80 ppm NO inhibits neointimal formation after balloon-induced carotid artery injury in rats. NO inhalation may represent a safe and novel method of preventing restenosis after percutaneous angioplasty.
Key Words: nitric oxide • neointimal formation • angioplasty • inhalation therapy
This article has been cited by other articles:
 |
|
 |
|
  X. Liu, Y. Huang, P. Pokreisz, P. Vermeersch, G. Marsboom, M. Swinnen, E. Verbeken, J. Santos, M. Pellens, H. Gillijns, et al. Nitric Oxide Inhalation Improves Microvascular Flow and Decreases Infarction Size After Myocardial Ischemia and Reperfusion J. Am. Coll. Cardiol., August 21, 2007; 50(8): 808 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hataishi, A. C. Rodrigues, T. G. Neilan, J. G. Morgan, E. Buys, S. Shiva, R. Tambouret, D. S. Jassal, M. J. Raher, E. Furutani, et al. Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H379 - H384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hataishi, W. M. Zapol, K. D. Bloch, and F. Ichinose Inhaled nitric oxide does not reduce systemic vascular resistance in mice Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1826 - H1829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. W. Q. Moore and D. Y. Hui Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthase J. Lipid Res., October 1, 2005; 46(10): 2083 - 2090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhuang, A.-C. Ceacareanu, B. Ceacareanu, and A. Hassid Essential role of protein kinase G and decreased cytoplasmic Ca2+ levels in NO-induced inhibition of rat aortic smooth muscle cell motility Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1859 - H1866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Dina, T. Feres, A. C.M. Paiva, and T. B. Paiva Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR Hypertension, January 1, 2004; 43(1): 131 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Maffia, A. Ianaro, R. Sorrentino, L. Lippolis, F. M. Maiello, P. del Soldato, A. Ialenti, and G. Cirino Beneficial Effects of NO-Releasing Derivative of Flurbiprofen (HCT-1026) in Rat Model of Vascular Injury and Restenosis Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 263 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, January 24, 2002; (2002) 22639399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. MacRitchie, K. H. Albertine, J. Sun, P. S. Lei, S. C. Jensen, A. A. Freestone, P. M. Clair, M. J. Dahl, E. A. Godfrey, D. P. Carlton, et al. Reduced endothelial nitric oxide synthase in lungs of chronically ventilated preterm lambs Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L1011 - L1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brown, Y. Lin, and A. Hassid Requirement of protein tyrosine phosphatase SHP2 for NO-stimulated vascular smooth muscle cell motility Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1598 - H1605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaul, B. Cercek, J. Rengstrom, X.-P. Xu, M. D. Molloy, P. Dimayuga, A. K. Parikh, M. C. Fishbein, J. Nilsson, T. B. Rajavashisth, et al. Polymeric-based perivascular delivery of a nitric oxide donor inhibits intimal thickening after balloon denudation arterial injury: role of nuclear factor-kappaB J. Am. Coll. Cardiol., February 1, 2000; 35(2): 493 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-Y. Chyu, P. Dimayuga, J. Zhu, J. Nilsson, S. Kaul, P. K. Shah, and B. Cercek Decreased Neointimal Thickening After Arterial Wall Injury in Inducible Nitric Oxide Synthase Knockout Mice Circ. Res., December 3, 1999; 85(12): 1192 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S Hayward, R. P Kelly, and P. S Macdonald Inhaled nitric oxide in cardiology practice Cardiovasc Res, August 15, 1999; 43(3): 628 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kibbe, T. Billiar, and E. Tzeng Inducible nitric oxide synthase and vascular injury Cardiovasc Res, August 15, 1999; 43(3): 650 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Veeramachaneni, A. H. Harken, and C. B. Cairns Clinical Implications of Hemoglobin as a Nitric Oxide Carrier Arch Surg, April 1, 1999; 134(4): 434 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Le Tourneau, E. Van Belle, D. Corseaux, B. Vallet, G. Lebuffe, B. Dupuis, J.-M. Lablanche, E. McFadden, C. Bauters, and M. E. Bertrand Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular remodeling J. Am. Coll. Cardiol., March 1, 1999; 33(3): 876 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fang, R. V. Sharma, and R. C. Bhalla Enhanced Recovery of Injury-Caused Downregulation of Paxillin Protein by eNOS Gene Expression in Rat Carotid Artery : Mechanism of NO Inhibition of Intimal Hyperplasia? Arterioscler. Thromb. Vasc. Biol., January 1, 1999; 19(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gries, C. Bode, K. Peter, A. Herr, H. Bohrer, J. Motsch, and E. Martin Inhaled Nitric Oxide Inhibits Human Platelet Aggregation, P-Selectin Expression, and Fibrinogen Binding In Vitro and In Vivo Circulation, April 21, 1998; 97(15): 1481 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. O. Han, D. S. Ettenson, E. W. Y. Koo, and E. R. Edelman Heparin/heparan sulfate chelation inhibits control of vascular repair by tissue-engineered endothelial cells Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2586 - H2595. [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]
|
|
|
|
|
|
S. Heeneman, J. F.M. Smits, P. J.A. Leenders, P. M.H. Schiffers, and M. J.A.P. Daemen Effects of Angiotensin II on Cardiac Function and Peripheral Vascular Structure During Compensated Heart Failure in the Rat Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 1985 - 1994. [Abstract] [Full Text]
|
|
|
|
|
|
C. Napoli, G. Aldini, J. L. Wallace, F. de Nigris, R. Maffei, P. Abete, D. Bonaduce, G. Condorelli, F. Rengo, V. Sica, et al. Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosis PNAS, February 5, 2002; 99(3): 1689 - 1694. [Abstract] [Full Text] [PDF]
|
|