| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA, USA
* To whom correspondence should be addressed. E-mail: spduckle{at}uci.edu.
Activation of inflammatory mechanisms contributes to cerebrovascular pathophysiology. Male gender is associated with increased stroke risk, yet little is known about effects of testosterone in the cerebral circulation. Therefore we explored the impact of testosterone treatment on cerebrovascular inflammation using both in vivo and in vitro models of inflammation. We hypothesized testosterone will augment the expression of two vascular markers of cellular inflammation: cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Using four groups of male rats (intact, orchiectomized (ORX), and ORX treated with either testosterone (ORXT) or the testosterone metabolite, 17
-estradiol (ORXE)), we determined effects of the sex hormones on cerebrovascular inflammation after i.p. lipopolysaccharide (LPS) injection. Western blot analysis showed that induction of inflammatory markers was increased in cerebral blood vessels from ORXT rats compared to intact or ORX males. In contrast, in cerebral blood vessels from ORXE rats, there was a significant decrease in endotoxin-induced COX-2 and iNOS protein levels. Confocal microscopy of cerebral blood vessels from ORXT rats showed increased COX-2 and iNOS immunoreactivity in both endothelial and smooth muscle cells after LPS treatment. In vitro incubation with LPS also induced COX-2 in pial vessels isolated from the four animal treatment groups, with the greatest induction observed in ORXT vessels as compared to the ORX and ORXE groups. Production of PGE2, a principal COX-2-derived prostaglandin end-product, was also greatest in isolated cerebral vessels from ORXT rats. In conclusion, testosterone increases cerebrovascular inflammation; this effect may contribute to stroke differences between men and women.
This article has been cited by other articles:
|
|
 |
|
  A. Razmara, L. Sunday, C. Stirone, X. B. Wang, D. N. Krause, S. P. Duckles, and V. Procaccio Mitochondrial Effects of Estrogen Are Mediated by Estrogen Receptor {alpha} in Brain Endothelial Cells J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 782 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sunday, C. Osuna, D. N. Krause, and S. P. Duckles Age alters cerebrovascular inflammation and effects of estrogen Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2333 - H2340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ashdown, S. Poole, P. Boksa, and G. N. Luheshi Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1667 - R1674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Krause, S. P. Duckles, and D. A. Pelligrino Influence of sex steroid hormones on cerebrovascular function J Appl Physiol, October 1, 2006; 101(4): 1252 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sunday, M. M. Tran, D. N. Krause, and S. P. Duckles Estrogen and progestagens differentially modulate vascular proinflammatory factors Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E261 - E267. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
