Circulation Research. 2002;90:602-608
Published online before print January 31, 2002, doi: 10.1161/01.RES.0000012202.52809.40
Published online before print January 31, 2002, doi: 10.1161/01.RES.0000012202.52809.40
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Integrative Physiology |
Inducible Nitric Oxide Synthase Modulates Cyclooxygenase-2 Activity in the Heart of Conscious Rabbits During the Late Phase of Ischemic Preconditioning
From the Experimental Research Laboratory, Division of Cardiology, University of Louisville and Jewish Hospital Heart and Lung Institute, Louisville, Ky.
Correspondence to Roberto Bolli, MD, Division of Cardiology, University of Louisville, Louisville, KY 40292. E-mail rbolli{at}louisville.edu
Cyclooxygenase-2 (COX-2) is known to mediate the cardioprotective effects of the late phase of ischemic preconditioning (PC); however, the signaling pathways involved in COX-2 induction following ischemic PC are unknown. In addition, although inducible nitric oxide synthase (iNOS) has been identified as a co-mediator of late PC together with COX-2, the interaction between iNOS and COX-2 in the heart is unknown. Using conscious rabbits, we found that the induction of COX-2 expression 24 hours after ischemic PC was blocked by pretreatment with inhibitors of protein kinase C (PKC), Src protein tyrosine kinases (PTKs), and nuclear factor-
B (NF-B) but not by inhibitors of NOS or scavengers of reactive oxygen species (ROS). The selective iNOS inhibitors SMT and 1400W, given 24 hours after PC, abrogated the increase in myocardial prostaglandin E2 (PGE2) and 6-keto-PGF1
, whereas the selective soluble guanylate cyclase inhibitor ODQ had no effect. COX-2 selective inhibitors (celecoxib and NS-398) did not affect iNOS activity. These results demonstrate that (i) ischemic PC upregulates cardiac COX-2 via PKC-, Src PTK-, and NF-B–dependent signaling pathways, whereas generation of NO and ROS is not necessary, and (ii) the activity of newly synthesized COX-2 following PC requires iNOS-derived NO whereas iNOS activity is independent of COX-2–derived prostanoids, indicating that COX-2 is located downstream of iNOS in the protective pathway of late PC. The data also indicate that iNOS modulates COX-2 activity via cGMP-independent mechanisms. To our knowledge, this is the first demonstration that iNOS-derived NO drives prostanoid synthesis by COX-2 in the heart. NO-mediated activation of COX-2 may be a heretofore unrecognized mechanism by which NO exerts its salubrious effects in the late phase of PC.
Key Words: prostaglandins • myocardial ischemia • reperfusion
This article has been cited by other articles:
 |
|
 |
|
  S. Korkmaz, T. Radovits, E. Barnucz, K. Hirschberg, P. Neugebauer, S. Loganathan, G. Veres, S. Pali, B. Seidel, S. Zollner, et al. Pharmacological Activation of Soluble Guanylate Cyclase Protects the Heart Against Ischemic Injury Circulation, August 25, 2009; 120(8): 677 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Jenkins, A. Cedars, and R. W. Gross Eicosanoid signalling pathways in the heart Cardiovasc Res, May 1, 2009; 82(2): 240 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Weber, J. Frassdorf, C. Ratajczak, Y. Grueber, W. Schlack, M. W. Hollmann, and B. Preckel Xenon Induces Late Cardiac Preconditioning In Vivo: A Role for Cyclooxygenase 2? Anesth. Analg., December 1, 2008; 107(6): 1807 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Pagel, J. G. Krolikowski, P. F. Pratt Jr, Y. H. Shim, J. Amour, D. C. Warltier, and D. Weihrauch The Mechanism of Helium-Induced Preconditioning: A Direct Role for Nitric Oxide in Rabbits Anesth. Analg., September 1, 2008; 107(3): 762 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ye, J. D. Martinez, R. J. Perez-Polo, Y. Lin, B. F. Uretsky, and Y. Birnbaum The role of eNOS, iNOS, and NF-{kappa}B in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H343 - H351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, K. Tamaki, K. Saito, Y. Nakano, T. Tobe, and R. Bolli Cardioprotective Effects of Short-Term Caloric Restriction Are Mediated by Adiponectin via Activation of AMP-Activated Protein Kinase Circulation, December 11, 2007; 116(24): 2809 - 2817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Carrier, I. Brochu, A. J. de Brum-Fernandes, and P. D'Orleans-Juste The Inducible Nitric-Oxide Synthase Modulates Endothelin-1-Dependent Release of Prostacyclin and Inhibition of Platelet Aggregation ex Vivo in the Mouse J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 972 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Joshi, R. Gertler, and R. Fricker Cardiovascular Thromboembolic Adverse Effects Associated with Cyclooxygenase-2 Selective Inhibitors and Nonselective Antiinflammatory Drugs Anesth. Analg., December 1, 2007; 105(6): 1793 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, W. Tan, Q. Ou, W.-J. Wu, D. Sturza, B. Dawn, G. Hunt, C. Cui, and R. Bolli Cardioprotection Afforded by Inducible Nitric Oxide Synthase Gene Therapy Is Mediated by Cyclooxygenase-2 via a Nuclear Factor-{kappa}B Dependent Pathway Circulation, October 2, 2007; 116(14): 1577 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sato, R. Bolli, G. D. Rokosh, Q. Bi, S. Dai, G. Shirk, and X.-L. Tang The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2557 - H2564. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shiva, M. N. Sack, J. J. Greer, M. Duranski, L. A. Ringwood, L. Burwell, X. Wang, P. H. MacArthur, A. Shoja, N. Raghavachari, et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer J. Exp. Med., September 3, 2007; 204(9): 2089 - 2102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli Preconditioning: a paradigm shift in the biology of myocardial ischemia Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H19 - H27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lee, B. Kosaras, H. Aleyasin, J. A. Han, D. S. Park, R. R. Ratan, N. W. Kowall, R. J. Ferrante, S. W. Lee, and H. Ryu Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response FASEB J, November 1, 2006; 20(13): 2375 - 2377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ye, Y. Lin, S. Atar, M.-H. Huang, J. R. Perez-Polo, B. F. Uretsky, and Y. Birnbaum Myocardial protection by pioglitazone, atorvastatin, and their combination: mechanisms and possible interactions Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1158 - H1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, P. C. Chiari, D. Weihrauch, J. G. Krolikowski, D. C. Warltier, J. R. Kersten, P. F. Pratt Jr, and P. S. Pagel Gender-specificity of delayed preconditioning by isoflurane in rabbits: potential role of endothelial nitric oxide synthase. Anesth. Analg., August 1, 2006; 103(2): 274 - 80, table of contents. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Atar, Y. Ye, Y. Lin, S. Y. Freeberg, S. P. Nishi, S. Rosanio, M.-H. Huang, B. F. Uretsky, J. R. Perez-Polo, and Y. Birnbaum Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2 Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1960 - H1968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Deng, S.-p. Zhao, H.-y. Dai, X.-s. Guan, and H.-g. Huang Atorvastatin Reduces the Expression of COX-2 mRNA in Peripheral Blood Monocytes from Patients with Acute Myocardial Infarction and Modulates the Early Inflammatory Response Clin. Chem., February 1, 2006; 52(2): 300 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wakeno-Takahashi, H. Otani, S. Nakao, H. Imamura, and K. Shingu Isoflurane induces second window of preconditioning through upregulation of inducible nitric oxide synthase in rat heart Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2585 - H2591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Zhu and X.-D. Tan TFF3 modulates NF-{kappa}B and a novel negative regulatory molecule of NF-{kappa}B in intestinal epithelial cells via a mechanism distinct from TNF-{alpha} Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1085 - C1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Abbate, R. Bussani, G. G.L. Biondi-Zoccai, D. Santini, A. Petrolini, F. D. Giorgio, F. Vasaturo, S. Scarpa, A. Severino, G. Liuzzo, et al. Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium Eur. Heart J., October 1, 2005; 26(19): 2039 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Gross, J. R. Falck, E. R. Gross, M. Isbell, J. Moore, and K. Nithipatikom Cytochrome P450 and arachidonic acid metabolites: Role in myocardial ischemia/reperfusion injury revisited Cardiovasc Res, October 1, 2005; 68(1): 18 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Xuan, Y. Guo, Y. Zhu, O.-L. Wang, G. Rokosh, R. O. Messing, and R. Bolli Role of the Protein Kinase C-{epsilon}-Raf-1-MEK-1/2-p44/42 MAPK Signaling Cascade in the Activation of Signal Transducers and Activators of Transcription 1 and 3 and Induction of Cyclooxygenase-2 After Ischemic Preconditioning Circulation, September 27, 2005; 112(13): 1971 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Minamoto, H. Harada, V. N. Lama, M. A. Fedarau, and D. J. Pinsky Reciprocal regulation of airway rejection by the inducible gas-forming enzymes heme oxygenase and nitric oxide synthase J. Exp. Med., July 18, 2005; 202(2): 283 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mollace, C. Muscoli, E. Masini, S. Cuzzocrea, and D. Salvemini Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors Pharmacol. Rev., June 1, 2005; 57(2): 217 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Jiang, E. Shi, Y. Nakajima, S. Sato, K. Ohno, and H. Yue Cyclooxygenase-1 Mediates the Final Stage of Morphine-Induced Delayed Cardioprotection in Concert With Cyclooxygenase-2 J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1707 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Virdis, R. Colucci, M. Fornai, C. Blandizzi, E. Duranti, S. Pinto, N. Bernardini, C. Segnani, L. Antonioli, S. Taddei, et al. Cyclooxygenase-2 Inhibition Improves Vascular Endothelial Dysfunction in a Rat Model of Endotoxic Shock: Role of Inducible Nitric-Oxide Synthase and Oxidative Stress J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 945 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Birnbaum, Y. Ye, S. Rosanio, S. Tavackoli, Z.-Y. Hu, E. R. Schwarz, and B. F. Uretsky Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury Cardiovasc Res, February 1, 2005; 65(2): 345 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamasowa, S. Shimizu, T. Inoue, M. Takaoka, and Y. Matsumura Endothelial Nitric Oxide Contributes to the Renal Protective Effects of Ischemic Preconditioning J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 153 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Stein, X.-L. Tang, Y. Guo, Y.-T. Xuan, B. Dawn, and R. Bolli Delayed Adaptation of the Heart to Stress: Late Preconditioning Stroke, November 1, 2004; 35(11_suppl_1): 2676 - 2679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Eltzschig and C. D. Collard Vascular ischaemia and reperfusion injury Br. Med. Bull., October 19, 2004; 70(1): 71 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, E. Kodani, J. Wang, S. X. Zhang, H. Takano, X.-L. Tang, and R. Bolli Cardioprotection During the Final Stage of the Late Phase of Ischemic Preconditioning Is Mediated by Neuronal NO Synthase in Concert With Cyclooxygenase-2 Circ. Res., July 9, 2004; 95(1): 84 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. FOGLI, P. NIERI, and M. C. BRESCHI The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage FASEB J, April 1, 2004; 18(6): 664 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Abbate, D Santini, G G L Biondi-Zoccai, S Scarpa, F Vasaturo, G Liuzzo, R Bussani, F Silvestri, F Baldi, F Crea, et al. Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe? Heart, April 1, 2004; 90(4): 440 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wu, A. P. Mannam, J. Wu, S. Kirbis, J.-L. Shie, C. Chen, R. J. Laham, F. W. Sellke, and J. Li Hypoxia induces myocyte-dependent COX-2 regulation in endothelial cells: role of VEGF Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2420 - H2429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Tsakadze, S. Srivastava, S. O. Awe, A. S. O. Adeagbo, A. Bhatnagar, and S. E. D'Souza Acrolein-induced vasomotor responses of rat aorta Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H727 - H734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Arnaud, M. Joyeux-Faure, D. Godin-Ribuot, and C. Ribuot COX-2: an in vivo evidence of its participation in heat stress-induced myocardial preconditioning Cardiovasc Res, June 1, 2003; 58(3): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, R. Vezza, T. Plappert, P. McNamara, J. A. Lawson, S. Austin, D. Pratico, M. S.-J. Sutton, and G. A. FitzGerald COX-2-Dependent Cardiac Failure in Gh/tTG Transgenic Mice Circ. Res., May 30, 2003; 92(10): 1153 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, Y.-T. Xuan, C. J. Lowenstein, S. C. Stevenson, S. D. Prabhu, W.-J. Wu, Y. Zhu, and R. Bolli Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2-Dependent Mechanism Circ. Res., April 18, 2003; 92(7): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, E. Kodani, Y. u-T. Xuan, B. Dawn, X.-L. Tang, and R. Bolli Effect of aspirin on late preconditioning against myocardial stunning in conscious rabbits J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1183 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Przyklenk and G. Heusch Late preconditioning against myocardial stunning: Does aspirin close the "second window" of endogenous cardioprotection? J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1195 - 1197. [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, M. Nagai, K. Tamaki, M. Tani, and R. Bolli COX-2-derived prostacyclin mediates opioid-induced late phase of preconditioning in isolated rat hearts Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2534 - H2543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kodani, Y.-T. Xuan, K. Shinmura, H. Takano, X.-L. Tang, and R. Bolli delta -Opioid receptor-induced late preconditioning is mediated by cyclooxygenase-2 in conscious rabbits Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1943 - H1957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli, K. Shinmura, X.-L. Tang, E. Kodani, Y.-T. Xuan, Y. Guo, and B. Dawn Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning Cardiovasc Res, August 15, 2002; 55(3): 506 - 519. [Abstract] [Full Text] [PDF]
|
|