Testosterone treatment enhances thromboxane A<sub>2</sub> mimetic induced coronary artery vasoconstriction in guinea pigs

Schrör, Karsten; Morinelli, Thomas A.; Masuda, Akira; Matsuda, Katsuhiro; Mathur, Rajesh S.; Halushka, Perry V.

doi:10.1111/j.1365-2362.1994.tb02428.x

Cited by 72 publications

(39 citation statements)

References 12 publications

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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: 68%

“…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). Interestingly, TP receptors in vascular tissue from males were more susceptible to testosterone modulation than those in female tissue (18,21,26).…”

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confidence: 99%

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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: 68%

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

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“…Conversely, alterations in pressor responses to pre-constricted isolated vessels following androgen treatment have also been reported in a few animal studies (Schrör et al 1994, Farhat et al 1995, Ceballos et al 1999, Quan et al 1999, Teoh et al 2000a. Ceballos et al (1999) exposed isolated coronary arteries from male rats to acute physiological concentrations of testosterone and demonstrated an attenuation of the vasodilatation induced by adenosine.…”

Section: Figurementioning

confidence: 74%

Testosterone: a vascular hormone in health and disease

Kelly¹,

Jones²

2013

Journal of Endocrinology

240

177

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Coronary heart disease is a leading cause of premature death in men. Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease (CVD). Furthermore, a low testosterone level is associated in some but not in all observational studies with an increase in cardiovascular events and mortality. Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation: key mediators of atherosclerosis. A bidirectional relationship between low endogenous testosterone levels and concurrent illness complicates attempts to validate causality in this association and potential mechanistic actions are complex. Testosterone is a vasoactive hormone that predominantly has vasodilatory actions on several vascular beds, although some studies have reported conflicting effects. In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure. Although the mechanism of the action of testosterone on vascular tone in vivo is not understood, laboratory research has found that testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells. Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis. The translational effects of testosterone between in vitro animal and human studies, some of which have conflicting effects, will be discussed in this review. We review the evidence for a role of testosterone in vascular health, its therapeutic potential and safety in hypogonadal men with CVD, and some of the possible underlying mechanisms.

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“…This may explain the higher responsiveness of male rat aortas to thromboxane A 2 compared to castrated males [58] . Testosterone increases thromboxane A 2 mimetic-mediated coronary artery constriction in guinea pigs in vivo and in vitro [60] . In rats inhibition of cytochrome P450 4A, which is expressed in vascular tissues and is stimulated by androgens, reduces production of 20-hydroxyeicosatetraenoic acid (20-HETE) [61] .…”

Section: Vascular Tonementioning

confidence: 94%

Testosterone and Blood Pressure Regulation

Kienitz

Quinkler

2008

Kidney Blood Press Res

113

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Background: There is substantial evidence that androgens may play a role in determining sex-specific blood pressure. Men are at higher risk for developing coronary heart disease or hypertension compared to premenopausal women. However, effects of androgens on the renal and cardiovascular system are complex. This review provides a critical overview of testosterone actions. Methods: We searched Pubmed library for experimental, animal and clinical studies, using the keywords ‘blood pressure’, ‘hypertension’, ‘testosterone’ and ‘androgens’. Results: While acute administration of testosterone seems to decrease vascular tone, the long-term net effect of androgens appears to be vasoconstriction via upregulation of thromboxane A₂ expression, norepinephrine synthesis, angiotensin II expression, and endothelin-1 action. Furthermore, androgens cause cardiac hypertrophy, promote atherosclerosis, vascular remodelling and stimulate renal prohypertensive processes involving the renin-angiotensin-aldosterone system. Androgens seem to promote oxidative stress in the kidney and may also play a role in the differentiation of brain areas involved in blood pressure regulation. Conclusion: The effects of sex steroids on different parts of the renal-vascular system are complex and often contradictory. In sum, net effects of androgen action seem to be vasoconstriction, atherosclerosis and stimulation of the renin-angiotensin-aldosterone system. Therefore, androgens may determine blood pressure and the prevalence of cardiovascular disease.

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Testosterone treatment enhances thromboxane A₂ mimetic induced coronary artery vasoconstriction in guinea pigs

Cited by 72 publications

References 12 publications

Testosterone treatment increases thromboxane function in rat cerebral arteries

Testosterone treatment increases thromboxane function in rat cerebral arteries

Testosterone: a vascular hormone in health and disease

Testosterone and Blood Pressure Regulation

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Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs

Cited by 72 publications

References 12 publications

Testosterone treatment increases thromboxane function in rat cerebral arteries

Testosterone treatment increases thromboxane function in rat cerebral arteries

Testosterone: a vascular hormone in health and disease

Testosterone and Blood Pressure Regulation

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Testosterone treatment enhances thromboxane A₂ mimetic induced coronary artery vasoconstriction in guinea pigs