Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia

Perusquı́a, Mercedes; Hanson, Andrea E.; Meza, Claudia; Kubli, Cris; Herrera, Nieves; Stallone, John N.

doi:10.1016/j.jsbmb.2017.11.001

Cited by 13 publications

(9 citation statements)

References 48 publications

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“…Particularly, 5β-DHT led to a substantial acute antihypertensive effect in hypertensive rats [123], which may be mainly due to a blockade of Ca 2+ entry through L-type VOCC [124]. Concerning the hypertensive disorders of pregnancy, Perusquia et al (2018) demonstrated, for the first time in a rat model of preeclampsia, that androgens, mainly DHEA and 5β-DHT, attenuate hypertension in vivo due to their vasorelaxant effect, and this is a nongenomic mediated response [125]. In conclusion, an excess or insufficient androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension.…”

Section: Testosterone and Blood Pressurementioning

confidence: 99%

“…Concerning the hypertensive disorders during pregnancy, it appears that T plays an important role in the pathogenesis of preeclampsia, [154]. An excess or insufficient androgen production during pregnancy may trigger the development of preeclampsia or gestational hypertension [125]. Thus, the scientific community believes that the administration of androgens in hypertensive disorders of pregnancy is a possibility, however, more clinical studies are needed.…”

Section: Potential Therapeutic Application Of Testosteronementioning

confidence: 99%

See 1 more Smart Citation

Vascular Pathways of Testosterone: Clinical Implications

Lorigo

Mariana

Oliveira

et al. 2019

J. of Cardiovasc. Trans. Res.

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Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Testosterone (T) is an important sex hormone that triggers several genomic and non-genomic pathways, leading to improvements of several cardiovascular risk factors and quality of life in men. At the vascular level, the key effect of T is the vasorelaxation. This review discusses the molecular pathways and clinical implications of T in the vascular system. Firstly, the mechanisms involved in the T vasodilator effect will be presented. Then, it will be discussed the association of T with the main risks for CVD, namely metabolic syndrome, type 2 diabetes mellitus, obesity, atherosclerosis, dyslipidaemia and hypertension. Several studies have shown a correlation between low T levels and an increased prevalence of several CVD. These observations suggest that T has beneficial effects on the cardiovascular system and that testosterone replacement therapy may become a therapeutic reality for some of these disorders.

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Section: Testosterone and Blood Pressurementioning

confidence: 99%

Section: Potential Therapeutic Application Of Testosteronementioning

confidence: 99%

Vascular Pathways of Testosterone: Clinical Implications

Lorigo

Mariana

Oliveira

et al. 2019

J. of Cardiovasc. Trans. Res.

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“…In 2018, Perusquía et al, using isolated thoracic aortas from pre-eclampsia-treated and normal pregnant rats previously treated with KCl or Phe, tested the cumulative concentrations (0.1–100 μM) of the androgens DHEA, 5α-DHT, 5β-DHT, and T, and found that T was able to induce vasorelaxation in both PE-treated and normal aortas treated with KCl, and less so in PE-treated aortas with Phe pre-treatment. Thus, the authors proved the vasorelaxant properties of T in the isolated maternal aortas of both PE and normal rat pregnancies [ 62 ].…”

Section: Effects Of Testosterone In Pre-eclampsiamentioning

confidence: 99%

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia

Fernandes,

Lorigo,

Cairrao

2024

CIMB

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Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men’s pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998–2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

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“…Many studies have linked the direct vasodilatory action of androgens in general, and 5β-DHT in particular, with the hypotensive/antihypertensive effects induced by these compounds in male [7,8,19,40] and female [52] animal models. Therefore, the effects of androgens on the vasodilator response to NO and CGRP have been analyzed.…”

Section: Plos Onementioning

confidence: 99%

“…On the other hand, and despite that the effect of 10 nM androgens on blood pressure has not been analyzed in the current investigation, the effect of the three androgens (at the particular concentration of 10 nM) on the vasomotor responses described in the present study appears to be due to the androgens-induced modification in cell signaling pathways [57,59,63] rather than the androgensinduced hypotension. This assumption, based on that the acute administration of androgens, at micromolar concentrations, has been demonstrated to induce hypotension in conscious rats [7,40,52]; this action was related to the non-genomic androgens-induced vasorelaxation, since in vagosympathectomized pithed rats (in which the participation of the central and autonomic nervous systems was excluded) androgens were also capable of inducing hypotension [18]. Additionally, in the present study -unlike the previous ones-, a lower concentration of androgens was used, therefore, it would be expected that the hypotensive effect induced by 10 nM androgens would be less than those reported for the micromolar concentration range.…”

Section: Plos Onementioning

confidence: 99%

Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

2021

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Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5β-dihydrotestosterone (5α- and 5β-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5β-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5β-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5β-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5β-DHT previously described in conscious SHR and WKY rats, pointing to 5β- DHT as a potential drug for the treatment of hypertension.

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Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia

Cited by 13 publications

References 48 publications

Vascular Pathways of Testosterone: Clinical Implications

Vascular Pathways of Testosterone: Clinical Implications

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia

Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

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