Published online before print June 3, 2002, doi: 10.1161/01.CIR.0000019408.67709.B5
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:3046.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Role of Cyclic Guanosine Monophosphate in Late Preconditioning in Conscious Rabbits
From the Experimental Research Laboratory, Division of Cardiology, University of Louisville and the Jewish 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
Background— Although NO has been shown to serve both as the trigger and the mediator of the late phase of ischemic preconditioning (PC), it is unknown whether NO acts via activation of soluble guanylate cyclase (sGC). The objective of this study was to investigate the role of sGC in late PC in conscious rabbits using the selective sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ).
Methods and Results— A total of 172 conscious rabbits were used. When nonpreconditioned rabbits were subjected to a sequence of 4-minute coronary occlusion/4-minute reperfusion cycles, myocardial cyclic guanosine monophosphate (cGMP) levels increased significantly at the end of the third and sixth occlusions. In rabbits preconditioned 24 hours earlier (on day 1) with six occlusion/reperfusion cycles, myocardial cGMP levels on day 2 were significantly higher than in nonpreconditioned rabbits even before ischemia but did not increase further during a second sequence of 4-minute occlusion/reperfusion cycles. Administration of ODQ before the six occlusion/reperfusion cycles on day 1 did not prevent the development of late PC against either stunning or infarction on day 2. In contrast, administration of ODQ on day 2 completely ablated the late PC effect against both stunning and infarction.
Conclusions— These results indicate that enhanced synthesis of cGMP by sGC is not necessary for ischemia to trigger a late PC effect but is required for the protection to become manifest 24 hours later. This implies that NO participates in late PC via two distinct mechanisms; ie, it triggers late PC on day 1 via a cGMP-independent mechanism and it mediates late PC on day 2 via a cGMP-dependent mechanism.
Key Words: ischemia • reperfusion • guanylate cyclase • cyclic guanosine monophosphate • oxadiazoles
This article has been cited by other articles:
 |
|
 |
|
  A. D.T. Costa, S. V. Pierre, M. V. Cohen, J. M. Downey, and K. D. Garlid cGMP signalling in pre- and post-conditioning: the role of mitochondria Cardiovasc Res, January 15, 2008; 77(2): 344 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Davidson and M. R. Duchen Effects of NO on mitochondrial function in cardiomyocytes: Pathophysiological relevance Cardiovasc Res, July 1, 2006; 71(1): 10 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Agullo, D. Garcia-Dorado, N. Escalona, M. Ruiz-Meana, M. Mirabet, J. Inserte, and J. Soler-Soler Membrane association of nitric oxide-sensitive guanylyl cyclase in cardiomyocytes Cardiovasc Res, October 1, 2005; 68(1): 65 - 74. [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]
|
|
|
|
|
|
R. C Kukreja, R. Ockaili, F. Salloum, and L. Xi Sildenafil-induced cardioprotection in rabbits Cardiovasc Res, December 1, 2003; 60(3): 700 - 701. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Agullo, D. Garcia-Dorado, N. Escalona, M. Ruiz-Meana, J. Inserte, and J. Soler-Soler Effect of ischemia on soluble and particulate guanylyl cyclase-mediated cGMP synthesis in cardiomyocytes Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2170 - H2176. [Abstract] [Full Text] [PDF]
|
|