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

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

doi:10.1038/s41440-024-01611-z

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

Hypertens Res. 2024 Feb 28. doi: 10.1038/s41440-024-01611-z. Online ahead of print.

Authors

Bruno Augusto Aguilar¹, Suenimeire Vieira¹, Ana Catarine Veiga¹, Joao Vitor Martins Bernal da Silva¹, Tallys Velasco Paixao¹, Karine Pereira Rodrigues¹, Jens Tank², Leticia Araujo Ruys¹, Hugo Celso Dutra de Souza³

Affiliations

¹ Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
² Department of Cardiovascular Aerospace Medicine, Institute of Aerospace Medicine, German Aerospace Center, 51147, Cologne, Germany.
³ Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. hugocds@fmrp.usp.br.

PMID: 38418900
DOI: 10.1038/s41440-024-01611-z

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.

Keywords: Aerobic physical training; Hypertension; Losartan; Sympathetic drive; Ventricular contractility.