Concurrent exercise training induces additional benefits to hydrochlorothiazide: Evidence for an improvement of autonomic control and oxidative stress in a model of hypertension and postmenopause

PLoS One. 2023 Aug 7;18(8):e0289715. doi: 10.1371/journal.pone.0289715. eCollection 2023.

Abstract

Objective: This study aimed to evaluate whether exercise training could contribute to a better modulation of the neurohumoral mechanisms linked to the pathophysiology of arterial hypertension (AH) in postmenopausal hypertensive rats treated with hydrochlorothiazide (HCTZ).

Methods: Female spontaneously hypertensive rats (SHR) (150-200g, 90 days old) were distributed into 5 hypertensive groups (n = 7-8 rats/group): control (C), ovariectomized (O), ovariectomized treated with HCTZ (OH), ovariectomized submitted to exercise training (OT) and ovariectomized submitted to exercise training and treated with HCTZ (OTH). Ovarian hormone deprivation was performed through bilateral ovariectomy. HCTZ (30mg/kg/day) and concurrent exercise training (3d/wk) were conducted lasted 8 weeks. Arterial pressure (AP) was directly recorded. Cardiac effort was evaluated using the rate-pressure product (RPP = systolic AP x heart rate). Vasopressin V1 receptor antagonist, losartan and hexamethonium were sequentially injected to evaluate the vasopressor systems. Inflammation and oxidative stress were evaluated in cardiac tissue.

Results: In addition to the reduction in AP, trained groups improved RPP, AP variability, bradycardic (OT: -1.3 ± 0.4 and OTH: -1.6 ± 0.3 vs. O: -0.6 ± 0.3 bpm/mmHg) and tachycardic responses of baroreflex sensitivity (OT: -2.4 ± 0.8 and OTH: -2.4 ± 0.8 vs. O: -1.3 ± 0.5 bpm/mmHg), NADPH oxidase and IL-10/TNF-α ratio. Hexamethonium injection revealed reduced sympathetic contribution on basal AP in OTH group (OTH: -49.8 ± 12.4 vs. O: -74.6 ± 18.1 mmHg). Furthermore, cardiac sympathovagal balance (LF/HF ratio), IL-10 and antioxidant enzymes were enhanced in OTH group. AP variability and baroreflex sensitivity were correlated with systolic AP, RPP, LF/HF ratio and inflammatory and oxidative stress parameters.

Conclusion: The combination of HCTZ plus concurrent exercise training induced additional positive adaptations in cardiovascular autonomic control, inflammation and redox balance in ovariectomized SHR. Therefore, combining exercise and medication may represent a promising strategy for managing classic and remaining cardiovascular risks in AH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baroreflex / physiology
  • Blood Pressure / physiology
  • Female
  • Heart Rate / physiology
  • Hexamethonium
  • Hydrochlorothiazide / pharmacology
  • Hypertension*
  • Inflammation
  • Interleukin-10
  • Oxidative Stress
  • Postmenopause*
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar

Substances

  • Interleukin-10
  • Hydrochlorothiazide
  • Hexamethonium

Grants and funding

MJF: 2019/06277-0, São Paulo Research Foundation (FAPESP) (https://fapesp.br/). KDA and MCI: National Council for Scientific and Technological Development (CNPq) (407398/2021-0; 406792/2022-4) (https://www.gov.br/cnpq/pt-br). Kátia De Angelis and Maria Claudia Irigoyen are recipients of CNPq Fellowship (CNPq-BPQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.