Jósvai Attila, Török Marianna, Hetthéssy Judit, Mátrai Máté, Monori-Kiss Anna, Makk Jennifer, Vezér Márton, Sára Levente, Szabó István, Székács Béla, Nádasy György L, Várbíró Szabolcs
Doctoral School of Theoretical and Translational Medicine, Semmelweis University, Budapest, Hungary.
Department of Neurosurgery, Hungarian Defense Forces Medical Centre, Budapest, Hungary.
Heliyon. 2022 Nov 11;8(11):e11533. doi: 10.1016/j.heliyon.2022.e11533. eCollection 2022 Nov.
Hypertension and andropause both accelerate age-related vascular deterioration. We aimed to evaluate the effects of angiotensin-II induced hypertension and deficiency of testosterone combined regarding the resistance coronaries found intramurally. Four male groups were formed from the animals: control group (Co, n = 10); the group that underwenr orchidectomy (ORC, n = 13), those that received an infusion of angiotensin-II (AII, n = 10) and a grous that received AII infusion and were also surgically orchidectomized (AII + ORC, n = 8). AII and AII + ORC animals were infused with infusing angiotensin-II (100 ng/min/kg) using osmotic minipumps. Orchidectomy was perfomed in the ORC and the AII + ORC groupsto establish deficiency regarding testosterone. Following four weeks of treatment, pressure-arteriography was performed in vitro, and the tone induced by administration of thromboxane-agonist (U46619) and bradykinin during analysis of the intramural coronaries (well-known to be resistance arterioles) was studied. U46619-induced vasoconstriction poved to be significantly decreased in the ORC and AII + ORC groups when compared with Co and AII animals. In ORC and AII + ORC groups, the bradykinin-induced relaxation was also significantly reduced to a greater extent compared to Co and AII rats. Following orchidectomy, the vasocontraction and vasodilatation capacity of blood vessels is reduced. The effect of testosterone deficiency on constrictor tone and relaxation remains pronounced even in AII hypertension: testosterone deficiency further narrows adaptation range in the double noxa (AII + ORC) group. Our studies suggest that vascular changes caused by high blood pressure and testosterone deficiency together may significantly increase age-related cardiovascular risk.
高血压和男性更年期都会加速与年龄相关的血管退化。我们旨在评估血管紧张素 II 诱导的高血压和睾酮缺乏联合作用对壁内阻力冠状动脉的影响。从这些动物中形成了四个雄性组:对照组(Co,n = 10);接受睾丸切除术的组(ORC,n = 13),接受血管紧张素 II 输注的组(AII,n = 10),以及接受血管紧张素 II 输注且同时接受手术睾丸切除术的组(AII + ORC,n = 8)。使用渗透微型泵向 AII 和 AII + ORC 组动物输注血管紧张素 II(100 ng/min/kg)。在 ORC 组和 AII + ORC 组中进行睾丸切除术以造成睾酮缺乏。治疗四周后,进行体外压力动脉造影,并在分析壁内冠状动脉(众所周知为阻力小动脉)期间研究给予血栓素激动剂(U46619)和缓激肽所诱导的张力。与 Co 组和 AII 组动物相比,ORC 组和 AII + ORC 组中 U46619 诱导的血管收缩明显降低。与 Co 组和 AII 组大鼠相比,ORC 组和 AII + ORC 组中缓激肽诱导的舒张也显著降低。睾丸切除术后,血管的血管收缩和血管舒张能力降低。即使在 AII 高血压中,睾酮缺乏对收缩张力和舒张的影响仍然显著:睾酮缺乏进一步缩小了双重损伤(AII + ORC)组的适应范围。我们的研究表明,高血压和睾酮缺乏共同引起的血管变化可能会显著增加与年龄相关的心血管风险。