Testosterone treatment increases thromboxane function in rat cerebral arteries

Rayna J Gonzales, Amir A. Ghaffari, Sue P. Duckles, Diana N. Krause

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We previously showed that testosterone, administered in vivo, increases the tone of cerebral arteries. A possible underlying mechanism is increased vasoconstriction through the thromboxane A2 (TxA2) pathway. Therefore, we investigated the effect of chronic testosterone treatment (4 wk) on TxA2 synthase levels and the contribution of TxA 2 to vascular tone in rat middle cerebral arteries (MCAs). Using immunofluorescence and confocal microscopy, we demonstrated that TxA2 synthase is present in MCA segments in both smooth muscle and endothelial layers. Using Western blot analysis, we found that TxA2 synthase protein levels are higher in cerebral vessel homogenates from testosterone-treated orchiectomized (ORX+T) rats compared with orchiectomized (ORX) control animals. Functional consequences of changes in cerebrovascular TxA2 synthase were determined using cannulated, pressurized MCA segments in vitro. Constrictor responses to the TxA2 mimetic U-46619 were not different between the ORX+T and ORX groups. However, dilator responses to either the selective TxA2 synthase inhibitor furegrelate or the TxA2-endoperoxide receptor (TP) antagonist SQ-29548 were greater in the ORX+T compared with ORX group. In endothelium-denuded arteries, the dilation to furegrelate was attenuated in both the ORX and ORX+T groups, and the difference between the groups was abolished. These data suggest that chronic testosterone treatment enhances TxA2-mediated tone in rat cerebral arteries by increasing endothelial TxA2 synthesis without altering the TP receptors mediating constriction. The effect of in vivo testosterone on cerebrovascular TxA2 synthase, observed here after chronic hormone administration, may contribute to the risk of vasospasm and thrombosis related to cerebrovascular disease.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number2 58-2
DOIs
StatePublished - Aug 2005
Externally publishedYes

Fingerprint

Thromboxane A2
Cerebral Arteries
Thromboxanes
Testosterone
Middle Cerebral Artery
Prostaglandin H2 Receptors Thromboxane A2
Thromboxane Receptors
Cerebrovascular Disorders
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Vasoconstriction
Fluorescence Microscopy
Constriction
Confocal Microscopy
Endothelium
Smooth Muscle
Blood Vessels
Dilatation
Thrombosis
Arteries
Western Blotting

Keywords

  • Cerebral circulation
  • Endothelium
  • Thromboxane synthase
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology

Cite this

Testosterone treatment increases thromboxane function in rat cerebral arteries. / Gonzales, Rayna J; Ghaffari, Amir A.; Duckles, Sue P.; Krause, Diana N.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 2 58-2, 08.2005.

Research output: Contribution to journalArticle

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