Orchidectomy increases the formation of non-endothelial thromboxane A2 and modulates its role in the electrical field stimulation-induced response in rat mesenteric artery

Abstract

The aim of this study was to analyze whether endogenous male sex hormones influence the release of thromboxane A 2 (TXA 2 ) and its role in the electrical field stimulation (EFS)-induced response, as well as the mechanism involved. For this purpose, endothelium-denuded mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used to measure TXA 2 release; EFS-induced response, nitric oxide (NO), norepinephrine (NA), and prostaglandin (PG) I 2 release were also measured in the presence of the TXA 2 synthesis inhibitor furegrelate. Orchidectomy increased basal and EFS-induced TXA 2 release. Furegrelate decreased the EFS-induced contraction in arteries from control rats, but did not modify it in arteries from orchidectomized rats. The EFS-induced neuronal NO release and vasodilator response were increased by furegrelate in arteries from control rats, but were not modified in arteries from orchidectomized rats. Furegrelate did not modify the EFS-induced NA release or vasoconstrictor response in arteries from either control or orchidectomized rats. The EFS-induced PGI 2 release was not modified by furegrelate in arteries from control rats, but was increased in arteries from orchidectomized rats. The results of the present study show that endogenous male sex hormone deprivation i) increases non-endothelial TXA 2 release and ii) regulates the effect of endogenous TXA 2 on the EFS-induced response through different mechanisms that, at the least, involve the NO and PGI 2 systems. In arteries from control rats, inhibition of TXA 2 formation decreases the EFS-induced response by increasing neuronal NO release. In arteries from orchidectomized rats, the EFS-induced response is unaltered after the inhibition of TXA 2 formation, by increasing PGI 2 release.

Docosahexaenoic Acid Supplemented Diet Influences the Orchidectomy-Induced Vascular Dysfunction in Rat Mesenteric Arteries

“…We observed that orchidectomy decreased the EFS-induced contraction, which is in agreement with that observed in mesenteric artery from 5 months-post-orchidectomized rats [13] in which the release of NA was not modified [18]. DHA-supplemented diet reversed the reduction in EFS-induced contractile response caused by orchidectomy.…”

“…In this regard, the contractile response induced by potassium depolarization was not altered by a DHA diet in hypertensive rats [37]. Although, we have previously reported that the orchidectomy did not modify the release of neuronal NO [13] and NA [18], it would have been desirable to determine the neurogenic release of NA and NO. The authors acknowledge this limitation of the current study and, because of the intriguing and complex interactions among the different factors, this issue will be addressed in future studies.…”

“…Regarding sex hormones, cardioprotective effects have been reported in men and women [2, 16]. Previous studies from our group have shown that the loss of gonadal function in male and female rats increased the release and function of vasoconstrictor prostanoids [17, 18], as well as the synthesis of ROS [13, 19, 20]. This accumulating production, when maintained for a significant amount of time, could lead to the development of cardiovascular diseases.…”

Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

“…It has been reported that TXA 2 is one of the most important vasoconstrictor prostanoids produced by the vascular wall that may participate in vascular dysfunction associated with cardiovascular risk factors [36]–[38]. We have already demonstrated that the release of TXA 2 was increased 5 months post-orchidectomy in mesenteric artery [9], [10], [19], probably as consequence of increased oxidative stress observed in these experimental conditions. To ascertain whether the release of TXA 2 also depends on the time lapsed since the gonadal function is lost, its release was also analyzed in vessels from 6 weeks post-orchidectomized rats.…”

“…These issues, as well as different mechanisms of action by which testosterone causes vasodilation were reviewed by Jones [7], In this regard, previous studies from our group have demonstrated an increase in the production of superoxide anion [8], prostanoids, such as thromboxane A 2 (TXA 2 ) [9], [10] and prostaglandin E 2 (PGE 2 ) [11] five months post-orchidectomy. Concerning the effect of androgens on endothelial NO release, most of studies were carried out in endothelial cells culture showing an increased release [12]–[14].…”