Testosterone Relaxes Isolated Human Radial Artery by Potassium Channel Opening Action

Seyrek, Melik; Yıldız, Oğuzhan; Ulusoy, Hasan; Yıldırım, Vedat

doi:10.1254/jphs.fp0060883

Cited by 60 publications

(51 citation statements)

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“…The newest large observational cohort with extended follow-up shows that normalization of total testosterone level after testosterone replacement therapy (TRT) is associated with a significant reduction in all-cause mortality, myocardial infarction, and stroke (Sharma et al 2015). The cardiovascular protective effects of testosterone partly attributes to its vasodilation effect and beneficial effect on blood lipid profile and against atheroma formation (Seyrek et al 2007;Yildiz and Seyrek 2007b). However, the underlying relevance of testosterone delaying vascular aging as well as cellular senescence remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Chen

Zhao

Jin

et al. 2016

AGE

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Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl-and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin IIinduced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin IIinduced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, AxlFc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/ FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.

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Section: Introductionmentioning

confidence: 99%

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Chen

Zhao

Jin

et al. 2016

AGE

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“…3,5,6 However, it does appear that this mechanism involves both local and central mechanisms. [7][8][9][10][11][12][13] Growth hormone (GH) levels, like testosterone, are also known to decline in an age-dependent manner. 14 This progressive decline has long been assumed to be physiological, although decline in GH secretion is associated with reduced lean body mass and bone density, an increased incidence of ischemic heart disease, dyslipidemia and erectile dysfunction, clinical outcomes that have also been observed in LOH.…”

Section: Introductionmentioning

confidence: 99%

IGF-1 levels are significantly correlated with patient-reported measures of sexual function

et al. 2011

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Growth hormone (GH) supplementation may help to preserve erectile function. We assessed whether serum insulin-like growth factor 1 (IGF-1) levels, a surrogate for GH levels, correlate with sexual function scores in 65 men who completed the Sexual Health Inventory for Men (SHIM) and Expanded Prostate Cancer Index Composite (EPIC) questionnaires, and had serum IGF-1 and testosterone levels determined. Median±s.d. IGF-1 level, SHIM and EPIC scores were 235.0±86.4, 19.5 ± 8.7 and 56.4 ± 28.3 mg ml À1 , respectively. IGF-1 levels and total SHIM score correlate significantly (r ¼ 0.31, P ¼ 0.02), as do IGF-1 levels and all individual SHIM question scores, and IGF-1 levels and the sexual domain of the EPIC questionnaire (r ¼ 0.30, P ¼ 0.02). No correlation was observed between IGF-1 levels and Gleason score, IGF-1 and testosterone level or SHIM score and testosterone level. These data support a potential role for the GH axis in erectile function.

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“…Lipidlowering and antioxidant effects of estrogen have been proposed to protect from the development of coronary artery disease (CAD) by many epidemiological and experimental studies. It is generally accepted that the incidence of morbidity and mortality from CAD depends on both gender and age (1,2). However, a woman and a man, aged around 65 years are similar in terms of cardiovascular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…Hypotestosteronemia in men for example, has been associated with CAD risk. Due to testosteroneinduced coronary vasodilatation testosterone replacement therapy appears to reverse CAD risk (2). Fibrinogen, plasminogen activator inhibitor-1, known as the risk factors for CAD, have also been found to be negatively correlated with serum testosterone levels (3).…”

Section: Introductionmentioning

confidence: 99%

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The effects of testosterone on isolated sheep coronary artery

Yıldırım¹,

Erol²

2011

Anadolu Kardiyol Derg

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ÖZETAmaç: Her ne kadar östrojenlerin vazoaktif etkileri olduğu gösterilmiş olsa da testosteronun vasküler etkileri iyi tanımlanmamıştır. Testosteronun in vitro izole damar preparatları üzerindeki etkileriyle ilgili bilgiler yeterli değildir. Bu deneysel prospektif çalışmanın amacı testosteronun in vitro olarak izole koyun koroner arteri üzerindeki doğrudan etkilerini değerlendirmekti. Yöntemler: Çalışmamızda testosteronun vasküler etkilerinin damar endotelinin var olup olmamasına, cinsiyet farklılığına veya uygulanan testosteron konsantrasyonuna bağlı olarak değişiklik gösterip göstermediğini araştırdık. Koroner arter halkalarının 30 mM KCl ile kasılması sağlandı. Kasılma cevapları plato düzeyine ulaştıktan sonra testosteron (10 -7 -10 -4 M ) kümülatif olarak uygulandı. Ayrıca testosterona bağlı cevaplar nitrik oksit sentez inhibitörü Nω-nitro-L-arginine methyl ester [L-NAME (10 -4 M)] ve L-arginin (10 -4 M) varlığında da değerlendirildi. İstatistiksel analizde ikili grupların karşılaştırılmasında Student's t-testi, çoklu grupların karşılaştırılmasında one way ANOVA testi kullanıldı. Bulgular: Testosteron koyun koroner arterlerinde gevşeme cevabı oluşturdu. Testosterona bağlı gevşeme cevapları cinsiyet [erkek endoteliyum (ME(+)): 24.48±4.13; -29.36±6.41; kadın endotelıyum (FE(-)): -3.02±1.04: p<0.05); (ME(+): -24.61±4.14; -24.48±4.13; -29.36±6.41; FE(-): -3.64±0.67: p<0.01); (FE(-):-4.91±0.67: p<0.001)] ve endotelle (ME(+): -9.23±2.4; FE(+): -6.33±1.5; -8.43±0.49; -8.83±0.9: p<0.05, p<0.01) ilişkili olarak değişiklik gösterdi. L-NAME testosterona bağlı gevşeme cevaplarını erkek [ME(+): 0.77±0.72; 0.086±0.012; 0.0768±0.083; 0.51±0.44: p<0.01, p<0.001] ve dişi (FE(+): 0.0318±0.052; 0.52±0.49; 0.029±70.05: p<0.05, p<0.001) endotelli gruplarda azaltırken sadece dişi endotelsiz (0.01±0.011; -1.14±0.59; ABSTRACTObjective: Although estrogens have been shown to be vasoactive hormones, the vascular effects of testosterone are not well defined. Little is known about the in vitro effects of testosterone on isolated arteries. The purpose of this experimental prospective study was to assess the direct effect of testosterone on isolated sheep coronary artery in vitro. Methods: We evaluated whether the vascular effects of testosterone were altered in the presence of endothelium or it changed in accordance to gender or the concentration of testosterone. Coronary arterial rings were precontracted by KCl (30mM). After plateau contraction levels were reached, testosterones (10 -7 -10 -4 M) were added in a cumulative manner. The effects of testosterone were also tested in the presence of NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 10 -4 M), and L-arginine (10 -4 M). In statistical analysis, Student's t-test was used for comparison between two groups and one-way ANOVA test for comparison among multiple groups. Results: Testosterone relaxed sheep coronary artery. Testosterone-induced relaxation was dependent of sex [male endothelium (ME(+)): 24.48±4.13; -29.36±6.41; female endothelium (FE(-)): -3.02±1.04: p<0.05); (ME(+):...

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Testosterone Relaxes Isolated Human Radial Artery by Potassium Channel Opening Action

Cited by 60 publications

References 45 publications

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

IGF-1 levels are significantly correlated with patient-reported measures of sexual function

The effects of testosterone on isolated sheep coronary artery

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