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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/H2444    most recent 01121.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Li, M. Articles by Stallone, J. N. Search for Related Content PubMed PubMed Citation Articles by Li, M. Articles by Stallone, J. N.

Estrogen potentiates constrictor prostanoid function in female rat aorta by upregulation of cyclooxygenase-2 and thromboxane pathway expression

¹Department of Veterinary Physiology and Pharmacology and ²Michael E. DeBakey Institute for Comparative Cardiovascular Science, College of Veterinary Medicine, Texas A&M University, College Station, Texas; and ³Department of Systems Biology and Translational Medicine, Texas A&M Health Sciences Center, Temple, Texas

Submitted 27 September 2007 ; accepted in final form 26 February 2008

Estrogen potentiates vascular reactivity to vasopressin (VP) by enhancing constrictor prostanoid function. To determine the cellular and molecular mechanisms, the effects of estrogen on arachidonic acid metabolism and on the expression of constrictor prostanoid pathway enzymes and endoperoxide/thromboxane receptor (TP) were determined in the female rat aorta. The release of thromboxane A₂ (TxA₂) and prostacyclin (PGI₂) was measured in male (M), intact-female (Int-F), ovariectomized-female (OvX-F), and OvX + 17β-estradiol-replaced female (OvX + ER-F) rats. The expression of mRNA for cyclooxygenase (COX)-1, COX-2, thromboxane synthase (TxS), and TP by aortic endothelium (Endo) and vascular smooth muscle (VSM) of these four experimental groups was measured by RT-PCR. The expression of COX-1, COX-2, and TxS proteins by Endo and VSM was also estimated by immunohistochemistry (IHC). Basal release of TxA₂ and PGI₂ was similar in M (18.8 ± 1.9 and 1,723 ± 153 pg/mg ring wt/45 min, respectively) and Int-F (20.2 ± 4.2 and 1,488 ± 123 pg, respectively) rat aortas. VP stimulated the dose-dependent release of TxA₂ and PGI₂ from both male and female rat aorta. OvX markedly attenuated and ER therapy restored VP-stimulated release of TxA₂ and PGI₂ in female rats. No differences in COX-1 mRNA levels were detected in either Endo or VSM of the four experimental groups (P > 0.1). The expression of both COX-2 and TxS mRNA were significantly higher (P < 0.05) in both Endo and VSM of Int-F and OvX + ER-F, compared with M or OvX-F. Expression of TP mRNA was significantly higher in VSM of Int-F and OvX + ER-F compared with M or OvX-F. IHC revealed the uniform staining of COX-1 in VSM of the four experimental groups, whereas staining of COX-2 and TxS was greater in Endo and VSM of Int-F and OvX + ER-F than in OvX-F or M rats. These data reveal that estrogen enhances constrictor prostanoid function in female rat aorta by upregulating the expression of COX-2 and TxS in both Endo and VSM and by upregulating the expression of TP in VSM.

arginine vasopressin; endothelium; thromboxane synthase; thromboxane receptor; vascular smooth muscle; vasoconstriction

This article has been cited by other articles:

				M. M. Sellers and J. N. Stallone Sympathy for the devil: the role of thromboxane in the regulation of vascular tone and blood pressure Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H1978 - H1986. [Abstract] [Full Text] [PDF]