Macedo Anderson G, Miotto Danyelle S, Tardelli Lidieli P, Santos Carlos F, Amaral Sandra L
Department of Physical Education, School of Sciences, São Paulo State University, Bauru, Brazil.
Joint Graduate Program in Physiological Sciences (PIPGCF), Federal University of São Carlos and São Paulo State University, São Carlos, Brazil.
Front Physiol. 2023 May 22;14:1147525. doi: 10.3389/fphys.2023.1147525. eCollection 2023.
Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some antihypertensive drugs attenuate this effect. This study compared the effects of captopril and perindopril on exercise-induced cardiac and skeletal muscle angiogenesis. Forty-eight Wistar rats and 48 SHR underwent 60 days of aerobic training or were kept sedentary. During the last 45 days, rats were treated with captopril, perindopril or water (Control). Blood pressure (BP) measurements were taken and histological samples from the tibialis anterior (TA) and left ventricle (LV) muscles were analyzed for capillary density (CD) and vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS) protein level. Exercise increased vessel density in Wistar rats due to higher VEGFR-2 (+17%) and eNOS (+31%) protein level. Captopril and perindopril attenuated exercise-induced angiogenesis in Wistar rats, but the attenuation was small in the perindopril group, and this response was mediated by higher eNOS levels in the Per group compared to the Cap group. Exercise increased myocardial CD in Wistar rats in all groups and treatment did not attenuate it. Both exercise and pharmacological treatment reduced BP of SHR similarly. Rarefaction was found in TA of SHR compared to Wistar, due to lower levels of VEGF (-26%) and eNOS (-27%) and treatment did not avoid this response. Exercise prevented these reductions in control SHR. While rats treated with perindopril showed angiogenesis in the TA muscle after training, those rats treated with captopril showed attenuated angiogenesis (-18%). This response was also mediated by lower eNOS levels in Cap group compared with Per and control group. Myocardial CD was reduced in all sedentary hypertensive compared with Wistar and training restored the number of vessels compared with sedentary SHR. In conclusion, taken into account only the aspect of vessel growth, since both pharmacological treatments reduced BP in SHR, the result of the present study suggests that perindopril could be a drug of choice over captopril for hypertensive practitioners of aerobic physical exercises, especially considering that it does not attenuate angiogenesis induced by aerobic physical training in skeletal and cardiac muscles.
血管生成是运动诱导的一种重要反应，可改善自发性高血压大鼠（SHR）的血流并降低血管阻力，但一些抗高血压药物会减弱这种作用。本研究比较了卡托普利和培哚普利对运动诱导的心脏和骨骼肌血管生成的影响。48只Wistar大鼠和48只SHR进行了60天的有氧训练或保持 sedentary状态。在最后45天，大鼠分别用卡托普利、培哚普利或水（对照）进行治疗。测量血压（BP），并分析来自胫前肌（TA）和左心室（LV）肌肉的组织学样本的毛细血管密度（CD）以及血管内皮生长因子（VEGF）、VEGF受体-2（VEGFR-2）和内皮型一氧化氮合酶（eNOS）蛋白水平。运动使Wistar大鼠的血管密度增加，这是由于VEGFR-2蛋白水平升高（+17%）和eNOS蛋白水平升高（+31%）。卡托普利和培哚普利减弱了Wistar大鼠运动诱导的血管生成，但培哚普利组的减弱程度较小，与卡托普利组相比，培哚普利组中较高的eNOS水平介导了这种反应。运动增加了所有组Wistar大鼠的心肌CD，且治疗并未减弱这种增加。运动和药物治疗对SHR血压的降低作用相似。与Wistar大鼠相比，SHR的TA中发现血管稀疏，这是由于VEGF水平降低（-26%）和eNOS水平降低（-27%），且治疗并未避免这种反应。运动可防止对照SHR出现这些降低。虽然培哚普利治疗的大鼠在训练后TA肌肉中出现血管生成，但卡托普利治疗的大鼠血管生成减弱（-18%）。与培哚普利组和对照组相比，卡托普利组中较低的eNOS水平也介导了这种反应。与Wistar大鼠相比，所有久坐的高血压大鼠的心肌CD均降低，与久坐的SHR相比，训练恢复了血管数量。总之，仅考虑血管生长方面，由于两种药物治疗均降低了SHR的血压，本研究结果表明，对于进行有氧体育锻炼的高血压患者，培哚普利可能是比卡托普利更好的选择，尤其是考虑到它不会减弱有氧体育训练诱导的骨骼肌和心肌血管生成。
