| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cardiology, Karolinska Hospital, Stockholm, Sweden
2 Center for metabolism and endocrinology, Huddinge University Hospital, Huddinge, Sweden
3 Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: adrian.gonon{at}medks.ki.se.
Endothelin (ET) receptor antagonism protects from ischemia-reperfusion injury. We hypothesized that the cardioprotective effect is related to nitric oxide (NO) bioavailability. Buffer-perfused rat and mouse hearts were subjected to ischemia and reperfusion. At the onset of ischemia the rat hearts received vehicle, the dual ETA/ETB receptor antagonist bosentan (10µM), the NO synthase inhibitor L-NMMA (100µM), the combination of bosentan and L-NMMA or the combination of bosentan, L-NMMA and the NO substrate L-arginine (1mM). Hearts from wild type and endothelial NO synthase (eNOS) deficient mice received either vehicle or bosentan. Myocardial performance, endothelial function, NO outflow and eNOS expression were monitored. Bosentan significantly improved myocardial function during reperfusion in rats and in wild type mice, but not in eNOS deficient mice. The functional protection afforded by bosentan was inhibited by L-NMMA, whereas it was restored by L-arginine. Myocardial expression of eNOS (immunoblotting) increased significantly in bosentantreated rat hearts in comparison with vehicle hearts. Recovery of NO outflow during reperfusion was enhanced in the bosentan treated rat heart. The endothelium-dependent vasodilator adenosine diphosphate increased coronary flow by 18±9% at the end of reperfusion in the bosentan group, whereas it reduced coronary flow by 7±5% in the vehicle group (P<0.001). The response to the endothelium-independent dilator sodium nitroprusside was not different between the two groups. In conclusion, the dual ETA/ETB receptor antagonist bosentan preserved endothelial and cardiac contractile function during ischemia and reperfusion via a mechanism dependent on endothelial NO production.
This article has been cited by other articles:
|
|
 |
|
  C. Jung, A. T. Gonon, P.-O. Sjoquist, J. O. Lundberg, and J. Pernow Arginase inhibition mediates cardioprotection during ischaemia-reperfusion Cardiovasc Res, September 18, 2009; (2009) cvp303v2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bohm and J. Pernow The importance of endothelin-1 for vascular dysfunction in cardiovascular disease Cardiovasc Res, October 1, 2007; 76(1): 8 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ramzy, V. Rao, L. C. Tumiati, N. Xu, R. Sheshgiri, J. Jackman, D. H. Delgado, and H. J. Ross Endothelin-1 accentuates the proatherosclerotic effects associated with C-reactive protein J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1137 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. McClintock, L. B. Ware, M. D. Eisner, N. Wickersham, B. T. Thompson, M. A. Matthay, and the National Heart, Lung, and Blood Institute ARDS Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung Injury Am. J. Respir. Crit. Care Med., February 1, 2007; 175(3): 256 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kolb-Bachofen, A. Kuhn, and C. V. Suschek The role of nitric oxide Rheumatology, October 1, 2006; 45(suppl_3): iii17 - iii19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ramzy, V. Rao, L. C. Tumiati, N. Xu, R. Sheshgiri, S. Miriuka, D. H. Delgado, and H. J. Ross Elevated Endothelin-1 Levels Impair Nitric Oxide Homeostasis Through a PKC-Dependent Pathway Circulation, July 4, 2006; 114(1_suppl): I-319 - I-326. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
