Jones Richard D, English Kate M, Pugh Peter J, Morice Alyn H, Jones T Hugh, Channer Kevin S
Academic Unit of Endocrinology, Division of Genomic Medicine, The University of Sheffield, UK.
J Cardiovasc Pharmacol. 2002 Jun;39(6):814-23. doi: 10.1097/00005344-200206000-00006.
Recent evidence supports a beneficial effect of testosterone on the cardiovascular system. Testosterone acts as a coronary vasodilator and reduces myocardial ischemia in men with coronary heart disease. The aim of the current study was to determine whether testosterone has a similar vasodilatory action in the pulmonary circulation and to characterize the underlying mechanism of action. The vasodilatory action of testosterone was studied in pulmonary arteries (n = 132, mean internal diameter = 344 +/- 8 microm) isolated from male rats (n = 48, mass = 396 +/- 7 g) mounted in a small vessel wire myograph and loaded to a tension equivalent to 17.5 mm Hg. Micromolar concentrations of testosterone induced dilatation in pulmonary arteries preconstricted with prostaglandin F2alpha (100 microM) within seconds of application. Dilatation to testosterone was similar in vessels treated with N-gamma-nitro-l-arginine methyl ester (l-NAME) (10 microM) or vehicle (5 microl distilled water), -38.2 +/- 2.9%, and -38.1 +/- 3.4%, respectively, and in vessels treated with indomethacin (10 microM), flutamide (10 microM), or vehicle (5 microl ethanol), -35.5 +/- 2.8%, -43.2 +/- 3.6%, and -35.7 +/- 4.6%, respectively (all p > 0.05). Maximal dilatation to testosterone occurred following preconstriction with agents that activated voltage-gated calcium channels such as prostaglandin F2alpha (-34.6 +/- 5.0%), BAY K8644 (-32.9 +/- 8.7), or potassium chloride (-26.7 +/- 1.5%), compared with calcium-independent protein kinase C activation by phorbol dibutyrate (-14.7 +/- 1.6%) or capacitative calcium entry via thapsigargin (-5.1 +/- 0.9%). This study demonstrates that testosterone induces pulmonary dilatation via a mechanism that is independent of the classic androgen receptor and also of the release of nitric oxide or dilator prostaglandins. The data support a calcium antagonistic action for testosterone in the pulmonary circulation, primarily against voltage-gated calcium channels.
近期证据支持睾酮对心血管系统具有有益作用。睾酮可作为冠状动脉血管扩张剂，减轻冠心病男性患者的心肌缺血。本研究的目的是确定睾酮在肺循环中是否具有类似的血管舒张作用，并阐明其潜在作用机制。在安装于小血管线肌张力测定仪上的雄性大鼠（n = 48，体重 = 396 ± 7 g）分离出的肺动脉（n = 132，平均内径 = 344 ± 8微米）中研究睾酮的血管舒张作用，并加载至相当于17.5毫米汞柱的张力。微摩尔浓度的睾酮在应用后数秒内即可使预先用前列腺素F2α（100微摩尔）收缩的肺动脉扩张。用N-γ-硝基-L-精氨酸甲酯（L-NAME）（10微摩尔）或溶媒（5微升蒸馏水）处理的血管对睾酮的扩张作用相似，分别为-38.2 ± 2.9%和-38.1 ± 3.4%，用吲哚美辛（10微摩尔）、氟他胺（10微摩尔）或溶媒（5微升乙醇）处理的血管对睾酮的扩张作用分别为-35.5 ± 2.8%、-43.2 ± 3.6%和-35.7 ± 4.6%（所有p > 0.05）。与佛波酯激活钙非依赖性蛋白激酶C（-14.7 ± 1.6%）或毒胡萝卜素介导的容量性钙内流（-5.1 ± 0.9%）相比，用激活电压门控钙通道的药物如前列腺素F2α（-34.6 ± 5.0%）、BAY K8644（-32.9 ± 8.7）或氯化钾（-26.7 ± 1.5%）预先收缩后，对睾酮的最大扩张作用出现。本研究表明，睾酮通过一种独立于经典雄激素受体以及一氧化氮或扩张性前列腺素释放的机制诱导肺血管扩张。数据支持睾酮在肺循环中具有钙拮抗作用，主要针对电压门控钙通道。
