Testosterone increases thromboxane A2 receptor density and responsiveness in rat aortas and platelets

Matsuda, Katsuhiro; Ruff, Albert; Morinelli, Thomas A.; Mathur, Rajesh S.; Halushka, Perry V.

doi:10.1152/ajpheart.1994.267.3.h887

Cited by 63 publications

(61 citation statements)

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“…However, concentration-response curves to the TP agonist U-46619 were identical in pressurized MCA segments from ORX and ORXϩT rats. This finding implies there was no change in cerebral artery TP receptors, in contrast with studies on other vascular beds, cultured vascular smooth muscle, and platelets in which testosterone increased TP receptor density and U-46619 responses (1,17,21,27,34). Because the mechanisms underlying testosterone effects on TP receptors are unknown, it is difficult at this point to explain why cerebral arteries differ.…”

Section: Discussionmentioning

confidence: 66%

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Testosterone treatment increases thromboxane function in rat cerebral arteries

Gonzales¹,

Ghaffari²,

Duckles³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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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 TxA2 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 TxA 2 synthase protein levels are higher in cerebral vessel homogenates from testosteronetreated orchiectomized (ORXϩT) 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 ORXϩT and ORX groups. However, dilator responses to either the selective TxA 2 synthase inhibitor furegrelate or the TxA2-endoperoxide receptor (TP) antagonist SQ-29548 were greater in the ORXϩT compared with ORX group. In endothelium-denuded arteries, the dilation to furegrelate was attenuated in both the ORX and ORXϩT groups, and the difference between the groups was abolished. These data suggest that chronic testosterone treatment enhances TxA 2-mediated tone in rat cerebral arteries by increasing endothelial TxA 2 synthesis without altering the TP receptors mediating constriction. The effect of in vivo testosterone on cerebrovascular TxA 2 synthase, observed here after chronic hormone administration, may contribute to the risk of vasospasm and thrombosis related to cerebrovascular disease. thromboxane synthase; cerebral circulation; vascular smooth muscle; endothelium ALTHOUGH THE RISK for cardiovascular disease and stroke is higher in males, the influence of testosterone on vascular function is not well understood (25). This lack of information also fuels concerns about the vascular impact of testosterone therapy for elderly men (33) and postmenopausal women (28) as well as the use of anabolic androgens in young athletes, both male and female (30). Androgens appear to influence a variety of cardiovascular risk factors including lipid profile, platelet aggregation, blood pressure, and vascular reactivity (1,25,31,44). Data on vascular reactivity, however, are limited and often conflicting. For example, acute exposure of arteries to testosterone has been found to cause either vasodilation or vasoconstriction (6,7,25,40,43), whereas chronic testosterone exposure in vivo results in increased vascular tone (13)(14)(15)31). A better understanding of how testosterone modulates vascular function is needed to explain these observations. In the cerebral circulation, the critical vascular bed in stroke, arterial tone is elevated after in vivo treatment with testosterone (14, 15, 31). Using rat middle cerebral arteries (MCAs), we demonstrated th...

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Section: Discussionmentioning

confidence: 66%

“…Testosterone was shown to increase the density of TxA 2 -endoperoxide receptors (TP) in platelets (1,27) and vascular smooth muscle cells cultured from the rat aorta or canine coronary artery (18,26). Testosterone also increased constrictor responses to the TxA 2 mimetic U-46619 in the isolated aorta and coronary and renal arteries (17,21,27,34).…”

mentioning

confidence: 99%

Testosterone treatment increases thromboxane function in rat cerebral arteries

Gonzales¹,

Ghaffari²,

Duckles³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

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“…Studies have shown that testosterone increases the levels of vascular smooth muscle thromboxane A 2 receptors in the aorta (28). Moreover, testosterone treatment enhances the vasoconstrictor response of thromboxane A 2 in the coronary circulation (21,28).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, testosterone treatment enhances the vasoconstrictor response of thromboxane A 2 in the coronary circulation (21,28). Furthermore, it has been shown that testosterone treatment inhibits prostacyclin synthesis in rat aorta smooth cells in culture (36).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of cardiac depression after trauma-hemorrhage: increased cardiomyocyte IL-6 and effect of sex steroids on IL-6 regulation and cardiac function

Yang¹,

Zheng²,

Hu³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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A prolonged depression of cardiovascular function occurs in males after trauma-hemorrhagic shock (T-H). Although a correlation between increased circulatory IL-6 levels and poor outcome has been reported after T-H, it remains unknown whether T-H increases IL-6 levels locally in cardiomyocytes and whether there is a correlation between altered cardiac function and local IL-6 production after T-H. T-H was induced in normal, castrated (2 wk before T-H), and 17β-estradiol (E2)-treated (0.5 mg sc, 1 wk before T-H) adult male rats. At 2 h after T-H or sham operation, cardiac output, heart rate, mean arterial pressure, positive and negative first derivative of pressure (±dP/d t), stroke volume, and total peripheral resistance were determined. Cardiomyocytes were isolated and divided into two parts: one was used for measurements of intracellular IL-6 levels using fluorescein-activated cell sorting, and the other was used to isolate RNA to determine IL-6 gene expression by quantitative real-time PCR. In addition, cardiac IL-6 protein levels were measured in freshly isolated hearts by Western blotting. Cardiac output, stroke volume, +dP/d t, −dP/d t, and total peripheral resistance were markedly altered after T-H. These parameters, except −dP/d t, improved significantly in the castrated group; however, all these parameters were restored in E2-treated males. Cardiomyocyte IL-6 mRNA expression and intracellular IL-6 production increased after T-H. Cardiac IL-6 protein levels increased after T-H in freshly isolated heart. Castration and E2 treatment attenuated cardiomyocyte intracellular IL-6 levels and cardiac IL-6 protein levels after T-H; however, only E2 treatment attenuated cardiomyocyte IL-6 gene expression. Thus there is an inverse correlation between cardiomyocyte IL-6 levels and cardiac function after T-H. The salutary effects of E2 on cardiac function after T-H may be due in part to decreased IL-6 synthesis in cardiomyocytes.

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“…However, endothelial injury as a result of lipid profile alterations and establishment of atherosclerosis could explain the impairment in endothelium-dependent pathway through decreased NO production. Also, the increase in TxA2 receptor density in vessel walls as a result of AAS treatment results in impaired endothelial-independent vasodilator pathways [50]. Further studies should be carried out to reveal more information on cellular and molecular processes related to the role of AAS on vasoreactivity.…”

Section: Impaired Vasodilatationmentioning

confidence: 99%