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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. General Cardiovascular Medicine
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1390547

Modulation of left ventricular hypertrophy in spontaneously hypertensive rats by acetylcholinesterase and ACE inhibitors: physiological, biochemical, and proteomic studies

Provisionally accepted
Lucie Hejnova Lucie Hejnova 1Zdenka Drastichova Zdenka Drastichova 1Almos Boroš Almos Boroš 2Jaroslav Hrdlicka Jaroslav Hrdlicka 3Michal Behuliak Michal Behuliak 2Jan Neckar Jan Neckar 2Josef Zicha Josef Zicha 2Jiri Novotny Jiri Novotny 1*
  • 1 Faculty of Science, Charles University, Prague, Prague, Czechia
  • 2 Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czechia
  • 3 Institute of Physiology, Academy of Sciences of the Czech Republic (ASCR), Prague, Prague, Czechia

The final, formatted version of the article will be published soon.

    The consequences at the molecular level and the mechanisms involved in a possible cardioprotective effect of antihypertensive treatment are not yet fully understood. Here, the efficacy of pyridostigmine (PYR) and trandolapril (TRA) as antihypertensive and antihypertrophic agents was investigated and compared in hypertensive SHR and normotensive WKY rats. In parallel, we investigated the effects of these drugs on myocardial β-adrenergic and cholinergic signaling pathways and protein expression profiles. Methods: Age-matched male SHR and WKY rats were chronically (8 weeks) treated with PYR or TRA in drinking water. Blood pressure (BP) and heart rate (HR) were monitored telemetrically prior to tissue sampling for biochemical analysis. Baroreceptor reflex sensitivity (BRS) and methylatropine HR response as a measure of vagal tone were evaluated in separate groups of animals. Results: PYR slightly lowered BP and HR in SHR rats during the dark phase of the day, while TRA effectively reduced BP during the light and dark phases without affecting HR. PYR enhanced BRS and improved vagal tone. There were no significant alterations in myocardial β-adrenergic and cholinergic signaling, with the exception of decreased forskolin-stimulated adenylyl cyclase (AC) activity in SHR rats, which was restored by TRA. Proteomic analysis revealed numerous differences induced by both treatments. Notable were changes in TGFβ-related signaling pathways as well as proteins involved in modifying hemodynamic parameters and cardiac hypertrophy. Conclusions: PYR is able to slightly decrease BP and HR in SHR rats but effectively increase BRS through vagal potentiation. The specific differences in protein expression profiles in rat myocardium

    Keywords: Acetylcholinesterase, cholinergic signaling, Hypertension, Shr and wky rats, myocardial proteome, Pyridostigmine, Trandolapril

    Received: 23 Feb 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Hejnova, Drastichova, Boroš, Hrdlicka, Behuliak, Neckar, Zicha and Novotny. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jiri Novotny, Faculty of Science, Charles University, Prague, 128 43, Prague, Czechia

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