Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery

Cairrão, Elisa; Álvarez, Ezequiel; Santos-Silva, António José; Verde, Ignácio

doi:10.1007/s00210-007-0213-3

Cited by 66 publications

(78 citation statements)

References 43 publications

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“…Therefore, it is reasonable to propose that 1) an insufficiency of androgens during pregnancy, particularly 5␤-DHT, could contribute, at least in part, to the development of preeclampsia/eclampsia and 2) exogenously administered 5␤-DHT may be therapeutically relevant for the treatment of gestational HT. Not only does Tes induce similar vasorelaxation in isolated vessels from women (2,48,55,71), but the female vasculature is also acutely sensitive to AR-independent vasodilation induced by 5␤-DHT (48), which also increases its potential for use as a safe antihypertensive in women.…”

Section: Physiological Relevancementioning

confidence: 94%

“…Figure 1 summarizes the possible nongenomic mechanisms of androgen action on the vascular wall. A variety of studies has demonstrated that the key mechanism underlying the vasorelaxing action of Tes is associated with the modulation of VSM cell membrane ion channel function, particularly 1) inactivation of L-type voltage-operated Ca 2ϩ channels (VOCCs) (6, 13, 17, 23, 24, 41-43, 48, 50, 59) or 2) activation of K ϩ channels (2,3,8,10,19,60,64,68,71,73), particularly the voltage-operated K ϩ channel (K v ) and/or the large-conductance Ca 2ϩ -activated K ϩ channel (BK Ca ).…”

Section: Mechanisms Of Androgen-induced Vasodilationmentioning

confidence: 99%

“…Indeed, numerous studies have now demonstrated that Tes exerts beneficial effects on cardiovascular function, among other effects, by inducing rapid vasorelaxation of vascular smooth muscle (VSM), as reviewed recently (44,66). This acute effect of Tes and other androgens has been observed at micromolar concentrations in a variety of large arteries (aorta, coronary and umbilical arteries) as well as small resistance arteries (mesenteric, prostatic, pulmonary, and subcutaneous) from several animal species (rat, mouse, rabbit, pig, and dog) and humans (2,8,10,32,48,60,71). Interestingly, in studies employing small vessel wire myography, it has been reported that micromolar concentrations of Tes induce vasodilation of rat pulmonary arteries (23), human subcutaneous resistance arterioles (32), and porcine small prostatic arteries (43).…”

mentioning

confidence: 96%

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Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

Perusquı́a

Stallone²

2010

American Journal of Physiology-Heart and Circulatory Physiology

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The marked sexual dimorphism that exists in human cardiovascular diseases has led to the dogmatic concept that testosterone (Tes) has deleterious effects and exacerbates the development of cardiovascular disease in males. While some animal studies suggest that Tes does exert deleterious effects by enhancing vascular tone through acute or chronic mechanisms, accumulating evidence suggests that Tes and other androgens exert beneficial effects by inducing rapid vasorelaxation of vascular smooth muscle through nongenomic mechanisms. While this effect frequently has been observed in large arteries at micromolar concentrations, more recent studies have reported vasorelaxation of smaller resistance arteries at nanomolar (physiological) concentrations. The key mechanism underlying Tes-induced vasorelaxation appears to be the modulation of vascular smooth muscle ion channel function, particularly the inactivation of L-type voltage-operated Ca(2+) channels and/or the activation of voltage-operated and Ca(2+)-activated K(+) channels. Studies employing Tes analogs and metabolites reveal that androgen-induced vasodilation is a structurally specific nongenomic effect that is fundamentally different than the genomic effects on reproductive targets. For example, 5alpha-dihydrotestosterone exhibits potent genomic-androgenic effects but only moderate vasorelaxing activity, whereas its isomer 5beta-dihydrotestosterone is devoid of androgenic effects but is a highly efficacious vasodilator. These findings suggest that the dihydro-metabolites of Tes or other androgen analogs devoid of androgenic or estrogenic effects could have useful therapeutic roles in hypertension, erectile dysfunction, prostatic ischemia, or other vascular dysfunctions.

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Section: Physiological Relevancementioning

confidence: 94%

Section: Mechanisms Of Androgen-induced Vasodilationmentioning

confidence: 99%

mentioning

confidence: 96%

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Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

Perusquı́a

Stallone²

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…The vasorelaxant effects of testosterone on human umbilical arteries, pre-contracted with serotonin or histamine or potassium chloride, were partially mediated by the activation of both voltage-sensitive K C channels and large-conductance, Ca 2C -activated K C channels (Cairrão et al 2008). This supports earlier animal studies that suggest that testosterone-induced vasorelaxation is mediated predominantly via K C channels in rat mesenteric arterial beds (Tep-areenan et al 2002), rabbit coronary arteries (Yue et al 1995) and rat aorta (Ding & Stallone 2001).…”

Section: Vascular Mechanisms Of Testosteronementioning

confidence: 99%

Testosterone: a vascular hormone in health and disease

Kelly¹,

Jones²

2013

Journal of Endocrinology

238

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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“…[106][107][108] The involvement of potassium channels in testosterone-induced vasodilatation has also been studied by many researchers. [109][110][111] Cairrao et al 112 reported that an AR antagonist, flutamide, and an adenosine triphosphate-sensitive potassium-channel inhibitor, glibenclamide, had no influence on the testosterone relaxant effect, whereas a voltage-sensitive potassium-channel inhibitor, 4-aminopyridine, decreased this effect of testosterone. Opening of voltage-sensitive potassium channels induces hyperpolarization of the plasma membrane, which in turn may lead to the closing of L-type Ca2+ channels.…”

Section: Effects Of Testosterone On Ecsmentioning

confidence: 99%

Hormonal effects on blood vessels

Akishita

2012

Hypertens Res

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The incidence of cardiovascular disease (CVD) is lower in younger women than in men of the same age, but it increases after menopause, implicating the atheroprotective action of endogenous estrogen. Although observational studies have suggested the efficacy of estrogen therapy in postmenopausal women, placebo-controlled, randomized trials, such as the Women's Health Initiative, have not confirmed effects of estrogen therapy on CVD. Conversely, basic, experimental research has progressed and provided mechanistic insight into estrogen's action on blood vessels. By contrast, the vascular effects of androgens remain poorly understood and have been controversial for a long time. In recent years, an increasing body of evidence has suggested that androgens may exert protective effects against the development of atherosclerosis, at least in elderly men. Epidemiological studies have shown that the incidence of and mortality due to CVD were increased in elderly men with low testosterone levels, although the efficacy of androgen therapy remains unknown. Furthermore, recent experimental studies have demonstrated the direct action of androgens on the vasculature. In this review, we illustrate the effects of sex steroids on the cardiovascular system, focusing on the action of testosterone on the blood vessels.

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Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery

Cited by 66 publications

References 43 publications

Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

Testosterone: a vascular hormone in health and disease

Hormonal effects on blood vessels

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