Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center, 51147, Cologne, Germany.
Hypertens Res. 2024 May;47(5):1350-1361. doi: 10.1038/s41440-024-01611-z. Epub 2024 Feb 28.
The treatment of hypertensive patients with losartan is very common. Despite the reduction in blood pressure, its effects on cardiac contractility and sympathetic autonomic drive are still controversial. In turn, aerobic physical training (APT) also presents an important therapeutic option, providing significant improvements in cardiovascular autonomic control, however little is known about its effects on cardiac contractility, especially when associated with losartan. Therefore, we investigated in spontaneously hypertensive rats (SHR) the effects of losartan and APT on cardiac hemodynamics and functionality, with emphasis on autonomic tonic balance and cardiac contractility. Sixty-four SHR (18 weeks old) were divided into four groups (N = 16): vehicle; vehicle submitted to APT through swimming for 12 weeks; treated with losartan (5 mg·kg·d) for 12 weeks; and treated with losartan associated with APT. The groups were submitted to cardiac morphological and functional analysis by echocardiography; double blockade of cardiac autonomic receptors with atropine and propranolol; and coronary bed reactivity and left ventricular contractility analyses by the Langendorff technique. APT improved functional parameters and autonomic balance by reducing sympathetic drive and/or increasing vagal drive. In contrast, it promoted a concentric remodeling of the left ventricle (LV). Treatment with losartan reduced sympathetic autonomic drive and cardiac morphological parameters, but there were no significant gains in cardiac functionality and contractility. When combined, the concentric remodeling of the LV to APT was abolished and gains in cardiac functionality and contractility were observed. Our findings suggest that the effects of losartan and APT are complementary and should be applied together in the treatment of hypertension. In spontaneously hypertensive rats, the combination of aerobic physical training with losartan treatment was crucial to greater blood pressure reductions and an increase in left ventricular contractility. Furthermore, losartan treatment prevented the concentric left ventricular remodeling caused by aerobic physical training.
用氯沙坦治疗高血压患者非常常见。尽管其降低血压的效果已得到证实,但它对心肌收缩力和交感自主神经驱动的影响仍存在争议。相反,有氧运动(APT)也提供了一种重要的治疗选择,可显著改善心血管自主神经控制,但对心肌收缩力的影响知之甚少,特别是当与氯沙坦联合使用时。因此,我们在自发性高血压大鼠(SHR)中研究了氯沙坦和 APT 对心脏血液动力学和功能的影响,重点关注自主紧张平衡和心肌收缩力。将 64 只 SHR(18 周龄)分为四组(N = 16):载体;通过游泳 12 周接受 APT 的载体;用氯沙坦(5mg·kg·d)治疗 12 周;并用氯沙坦联合 APT 治疗。通过超声心动图对各组进行心脏形态和功能分析;用阿托品和普萘洛尔双重阻断心脏自主受体;通过 Langendorff 技术分析冠状血管床反应性和左心室收缩性。APT 通过降低交感神经驱动和/或增加迷走神经驱动来改善功能参数和自主平衡。相反,它促进了左心室(LV)的向心性重构。用氯沙坦治疗可降低交感自主神经驱动和心脏形态参数,但对心脏功能和收缩性没有明显改善。联合应用时,LV 的向心性重构被消除,并观察到心脏功能和收缩性的改善。我们的研究结果表明,氯沙坦和 APT 的作用是互补的,应该一起用于高血压的治疗。在自发性高血压大鼠中,有氧运动与氯沙坦联合治疗对降低血压和增加左心室收缩力至关重要。此外,氯沙坦治疗可预防有氧运动引起的左心室向心性重构。