| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1Department of Physiology, New York Medical College, Valhalla, New York; and 2Xuzhou Medical College, Xuzhou, People's Republic of China
Submitted 25 October 2005 ; accepted in final form 5 April 2006
Our previous studies demonstrated that, in gracilis muscle arterioles of male mice deficient in the gene for endothelial nitric oxide synthase (eNOS), flow-induced dilation (FID) is mediated by endothelial PGs. Thus the present study aimed to identify the specific isoform of cyclooxygenase (COX) responsible for the compensatory mediation of FID in arterioles of eNOS-knockout (KO) mice. Experiments were conducted on gracilis muscle arterioles of male eNOS-KO and wild-type (WT) mice. Basal tone and magnitude of FID of arterioles were comparable in the two strains of mice. A role for COX isoforms in the mediation of the responses was assessed by use of valeryl salicylate (3 mM) and NS-398 (10 µM), inhibitors of COX-1 and COX-2, respectively. In eNOS-KO arterioles, valeryl salicylate or NS-398 alone inhibited FID (at maximal flow rate) by 
51% and 58%, respectively. Administration of both inhibitors eliminated the dilation. In WT arterioles, inhibition of COX-2 did not significantly affect FID, whereas inhibition of COX-1 decreased the dilation by 57%. The residual portion of the response was abolished by additional administration of N
-nitro-L-arginine methyl ester. Western blot analysis indicated a comparable content of COX-1 protein in arterioles of WT and eNOS-KO mice. COX-2 protein, which was not detectable in arterioles of WT mice, was strongly expressed in arterioles of eNOS-KO mice, together with an upregulation of COX-2 gene expression. Immunohistochemical staining confirmed the presence of COX-2 in the endothelium of eNOS-KO arterioles. In conclusion, COX-2-derived PGs are the mediators responsible for maintenance of FID in arterioles of eNOS-deficient mice.
nitric oxide; endothelium
This article has been cited by other articles:
|
|
 |
|
  J. L. Park, L. Shu, and J. A. Shayman Differential involvement of COX1 and COX2 in the vasculopathy associated with the {alpha}-galactosidase A-knockout mouse Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1133 - H1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dumont, F. Pinaud, A.-L. Guihot, C. Baufreton, L. Loufrani, and D. Henrion Alteration in flow (shear stress)-induced remodelling in rat resistance arteries with aging: improvement by a treatment with hydralazine Cardiovasc Res, February 1, 2008; 77(3): 600 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Haas, J. L. Doyle, M. R. Distasi, L. E. Norton, K. M. Sheridan, and J. L. Unthank Involvement of MMPs in the outward remodeling of collateral mesenteric arteries Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2429 - H2437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Focardi, G. M. Dick, A. Picchi, C. Zhang, and W. M. Chilian Restoration of coronary endothelial function in obese Zucker rats by a low-carbohydrate diet Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2093 - H2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Anning, B. Coles, J. Morton, H. Wang, J. Uddin, J. D. Morrow, S. K. Dey, L. J. Marnett, and V. B. O'Donnell Nitric oxide deficiency promotes vascular side effects of cyclooxygenase inhibitors Blood, December 15, 2006; 108(13): 4059 - 4062. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
