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睾酮对离体绵羊冠状动脉的影响。

The effects of testosterone on isolated sheep coronary artery.

作者信息

Yıldırım Engin, Erol Kevser

机构信息

Department of Pharmacology, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir-Turkey.

出版信息

Anadolu Kardiyol Derg. 2011 Jun;11(4):343-50. doi: 10.5152/akd.2011.086. Epub 2011 May 11.

Abstract

OBJECTIVE

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 (30 mM). 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, 10-4M), 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(+): -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)] and endothelium (ME(+): -9.23±2.4; FE(+): -6.33±1.5; -8.43±0.49; -8.83±0.9: p<0.05, p<0.01). L-NAME decreased relaxations in the male (ME(+): 0.77±0.72; 0.086±0.012; 0.0768±0.083; 0.51±0.44: p<0.01, p<0.001) and female (FE(+): 0.0318±0.052; 0.52±0.49; 0.029±70.05: p<0.05, p<0.001) with endothelium groups but only female without (0.01±0.011; -1.14±0.59; -1.23±1.21: p<0.01, p<0.001) endothelium group. L-arginine decreased relaxations especially in the male with endothelium (ME(+): -1.7±0.91; -3.02±1.42; -2.51±1.46; -6.68±2.15; p<0.01, p<0.001) group and in part in the female with (FE(+):-1.73±0.83; p<0.05) or without (FE(-): -1.14±0.59; p<0.01) endothelium groups.

CONCLUSION

Testosterone induces endothelium and sex-dependent relaxation on sheep coronary artery in vitro. Acute testosterone-induced coronary vasodilatation is mediated in part via endothelium-derived NO. Non-genomic mechanisms may be considered to play a role in the vasodilatory effect of testosterone especially in the female group.

摘要

目的

尽管雌激素已被证明是血管活性激素,但睾酮对血管的作用尚不明确。关于睾酮对离体动脉的体外作用知之甚少。本实验前瞻性研究的目的是评估睾酮对离体绵羊冠状动脉的直接作用。

方法

我们评估了在有内皮的情况下睾酮的血管作用是否改变,或者其是否根据性别或睾酮浓度而变化。冠状动脉环用氯化钾(30 mM)预收缩。达到平台收缩水平后,以累积方式添加睾酮(10⁻⁷ - 10⁻⁴M)。还在一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME,10⁻⁴M)和L-精氨酸(10⁻⁴M)存在的情况下测试睾酮的作用。在统计分析中,两组之间的比较采用学生t检验,多组之间的比较采用单向方差分析。

结果

睾酮使绵羊冠状动脉舒张。睾酮诱导的舒张依赖于性别[雄性内皮(ME(+)):24.48±4.13; -29.36±6.41;雌性内皮(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)]和内皮(ME(+): -9.23±2.4;FE(+): -6.33±1.5; -8.43±0.49; -8.83±0.9:p<0.05,p<0.01)。L-NAME降低了有内皮组雄性(ME(+):0.77±0.72;0.086±0.012;0.0768±0.083;0.51±0.44:p<0.01,p<0.001)和雌性(FE(+):0.0318±0.052;0.52±0.49;0.029±70.05:p<0.05,p<0.001)的舒张,但仅降低了无内皮组雌性(0.01±0.011; -1.14±0.59; -1.23±1.21:p<0.01,p<0.001)的舒张。L-精氨酸降低了舒张,尤其是有内皮组雄性(ME(+): -1.7±0.91; -3.02±1.42; -2.51±1.46; -6.68±2.15;p<0.01,p<0.001)组以及部分有(FE(+):-1.73±0.83;p<0.05)或无(FE(-): -1.14±0.59;p<0.01)内皮组的雌性。

结论

睾酮在体外对绵羊冠状动脉具有内皮和性别依赖性舒张作用。急性睾酮诱导的冠状动脉舒张部分通过内皮衍生的一氧化氮介导。非基因组机制可能在睾酮的血管舒张作用中起作用,尤其是在雌性组中。

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