Endogenous testosterone increases leukocyte–endothelial cell interaction in spontaneously hypertensive rats

Filgueira, Fernando; Lobato, Núbia de Souza; DosSantos, Rosangela A.; Oliveira, Maria Aparecida de; Akamine, Eliana Hiromi; Tostes, Rita C.; Fortes, Zuleica Bruno; Carvalho, Maria Helena Catelli de

doi:10.1016/j.lfs.2012.03.009

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…Previous reports from our group showed that testosterone does not alter venular diameter, blood flow velocity, shear rate and leucocyte velocity in the vascular bed studied in the present study (mesentery bed) [13], making unlikely the possibility that changes in venular parameters or leucocyte velocity are involved in the effects of testosterone on leucocytes migration. The fact that this effect could be observed only 24 h after testosterone administration together with the finding that flutamide blocks testosterone-induced leucocyte migration indicates that this effect occurs via genomic pathways, probably by indirect mechanisms.…”

Section: Discussioncontrasting

confidence: 63%

“…Previous work from our group reported that endogenous testosterone can partly modulate early leucocyte-endothelial cell interactions in SHR [13]. Castrated SHR had lower numbers of rolling leucocytes when compared with non-castrated animals.…”

Section: Discussionmentioning

confidence: 68%

“…The effects of testosterone on inflammatory processes are not fully understood and this steroid hormone has been shown to have both pro- [13] and anti-inflammatory [14] actions. In addition, it is unknown whether testosterone-induced ROS generation can also trigger inflammatory processes, which would further contribute to testosterone-induced vascular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms

et al. 2015

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The mechanisms whereby testosterone increases cardiovascular risk are not clarified. However, oxidative stress and inflammation seem to be determinants. Herein, we sought to determine whether exogenous testosterone, at physiological levels, induces leucocyte migration, a central feature in immune and inflammatory responses and the mediating mechanisms. We hypothesized that testosterone induces leucocyte migration via NADPH oxidase (NADPHox)-driven reactive oxygen species (ROS) and cyclooxygenase (COX)-dependent mechanisms. Sixteen-week-old Wistar rats received an intraperitoneal injection (5 ml) of either testosterone (10(-7) mol/l) or saline. Rats were pre-treated with 5 ml of sodium salicylate (SS, non-selective COX inhibitor, 1.25 × 10(-3) mol/l, 1 h prior to testosterone or saline), flutamide (androgen receptor antagonist, 10(-5) mol/l), apocynin (NADPHox inhibitor, 3 × 10(-4) mol/l), N-[2-Cyclohexyloxy-4-nitrophenyl]methanesulfonamide (NS398, COX2 inhibitor, 10(-4) mol/l) or saline, 4 h before testosterone or saline administration. Leucocyte migration was assessed 24 h after testosterone administration by intravital microscopy of the mesenteric bed. Serum levels of testosterone were measured by radioimmunoassay. NADPHox activity was assessed in membrane fractions of the mesenteric bed by dihydroethidium (DHE) fluorescence and in isolated vascular smooth muscle cells (VSMC) by HPLC. NADPHox subunits and VCAM (vascular cell adhesion molecule) expression were determined by immunoblotting. Testosterone administration did not change serum levels of endogenous testosterone, but increased venular leucocyte migration to the adventia, NADPHox activity and expression (P < 0.05). These effects were blocked by flutamide. SS inhibited testosterone-induced leucocyte migration (P<0.05). Apocynin and NS398 abolished testosterone-induced leucocyte migration and NADPHox activity (P<0.05). Testosterone induces leucocyte migration via NADPHox- and COX2-dependent mechanisms and may contribute to inflammatory processes and oxidative stress in the vasculature potentially increasing cardiovascular risk.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms

et al. 2015

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“…In addition, testosterone is a potential neuroprotective factor against the inflammation associated with neurodegenerative disorders, such as Alzheimer’s disease ( 66 ) and multiple sclerosis ( 67 ). However, this literature is confounded by mixed results, with studies showing either no ( 60 ) or a positive correlation of testosterone levels and inflammation markers ( 68 ). As well as testosterone, estrogens have also been depicted as neuroprotective and/or anti-inflammatory agents.…”

Section: Neuroinflammation and Steroidal Hormonesmentioning

confidence: 99%

The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions

et al. 2016

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Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain. The hypothalamic–pituitary–adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer’s and Parkinson’s diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, while metabolic syndromes, such as diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, such as calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes.

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“…The effects of testosterone on blood pressure regulation have been documented in animals. In hypertensive rats, the levels of testosterone correlate with the mean arterial pressure (MAP) (10,15,23,27,37). However, in some studies, testosterone was found to have no effect on the blood pressure (8,17).…”

Section: Introductionmentioning

confidence: 99%

Influence of testosterone on mean arterial pressure: A physiological study in male and female normotensive WKY and hypertensive SHR rats

Loh

Salleh

2017

Physiol. Int.

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Introduction Testosterone plays an important role in the blood pressure regulation. However, information with regard to the effect of this hormone on blood pressure in normotensive and hypertensive conditions is limited. Therefore, in this study, the relationship between plasma testosterone level and mean arterial pressure (MAP) was investigated under these conditions. Methods Normotensive Wistar-Kyoto (WKY) and hypertensive Spontaneous Hypertensive (SHR) male and female rats were gonadectomized with female rats treated with testosterone. Estrous cycle stages of intact female rats of both strains were identified by vaginal smear. Pressure in the carotid artery of anesthetized rats was measured via direct cannulation technique. The blood was withdrawn for plasma testosterone level measurement by enzyme-linked immunosorbent assay. Results Treatment of ovariectomized female WKY and SHR rats with testosterone for 6-week duration has resulted in MAP to increase (P < 0.05). In male WKY and SHR rats, MAP and plasma testosterone levels decreased by orchidectomy (P < 0.05). No significant differences in MAP and plasma testosterone levels were observed in intact female WKY and SHR rats between stages of the estrous cycle. Conclusions The effects seen in testosterone-treated ovariectomized female rats and in orchidectomized male rats suggested that testosterone could play an important role in causing the blood pressure to increase.

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Endogenous testosterone increases leukocyte–endothelial cell interaction in spontaneously hypertensive rats

Cited by 10 publications

References 34 publications

Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms

Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms

The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions

Influence of testosterone on mean arterial pressure: A physiological study in male and female normotensive WKY and hypertensive SHR rats

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