Rouver Wender Nascimento, Delgado Nathalie Tristão Banhos, Menezes Jussara Bezerra, Santos Roger Lyrio, Moyses Margareth Ribeiro
Department of Physiological Sciences, Federal University of Espírito Santo (Universidade Federal do Espírito Santo-UFES), Vitória, Brazil.
PLoS One. 2015 Aug 31;10(8):e0137111. doi: 10.1371/journal.pone.0137111. eCollection 2015.
The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP.
本研究旨在确定不同剂量睾酮长期治疗对雄性大鼠内皮依赖性冠状动脉血管反应性的影响。成年雄性大鼠被分为四个实验组:对照组(假手术组,SHAM)、去势组(CAST)、去势后立即皮下注射生理剂量(0.5毫克/千克/天,生理组,PHYSIO)或超生理剂量(2.5毫克/千克/天,超生理组,SUPRA)睾酮,持续15天。治疗结束时通过尾容积描记法评估收缩压(SBP)。安乐死后,取出心脏,采用Langendorff逆行灌注技术评估冠状动脉血管反应性。构建缓激肽(BK)的剂量反应曲线,随后用100微摩尔/升L-精氨酸甲酯(L-NAME)、2.8微摩尔/升吲哚美辛(INDO)、L-NAME + INDO或L-NAME + INDO + 0.75微摩尔克霉唑(CLOT)进行抑制。我们观察到显著的内皮依赖性、BK诱导的冠状动脉血管舒张,去势组这种舒张消失,而生理组和超生理组恢复。此外,去势改变了脂质和激素谱并降低了体重,睾酮治疗恢复了所有这些参数。我们的结果显示超生理组SBP升高。此外,我们的数据使我们得出结论,生理浓度的睾酮可能通过维持有利于内皮依赖性血管舒张剂活性的环境而不增加SBP,从而在心血管系统中发挥有益作用。