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Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan

Hypertension Research volume 47, pages 1350–1361 (2024)Cite this article

Abstract

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−1·d−1) 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.

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Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001, and by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) – Finance Code 2022/02006-5 and 2021/14938-7.

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  1. Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Bruno Augusto Aguilar, Suenimeire Vieira, Ana Catarine Veiga, Joao Vitor Martins Bernal da Silva, Tallys Velasco Paixao, Karine Pereira Rodrigues, Leticia Araujo Ruys & Hugo Celso Dutra de Souza

  2. Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center, 51147, Cologne, Germany

    Jens Tank

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  1. Bruno Augusto Aguilar
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BAA, SV, and HCDS conceived and designed research; SV, BAA, and KPR performed experiments; BAA, SV, and HCDS analyzed data; BAA, SV, JT, and HCDS interpreted results of experiments; ACV, JVMBS, and TEVP prepared figures; BAA, ACV, and HCDS drafted manuscript; HCDS, BAA, and JT edited and revised manuscript; BAA, SV, ACV, JVMBS, TEVP, KPR, JT, and HCDS approved final version of manuscript.

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Aguilar, B.A., Vieira, S., Veiga, A.C. et al. Physical exercise is essential for increasing ventricular contractility in hypertensive rats treated with losartan. Hypertens Res 47, 1350–1361 (2024). https://doi.org/10.1038/s41440-024-01611-z

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