Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol fed rats

Role of polyprenyl derivatives and nitric oxide

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Abstract

We have previously shown that hypercholesterolemia leads to the loss of pacing-induced preconditioning (PC), possibly due to the impairment of cardiac nitric oxide (NO) synthesis. It has been shown that excess exogenous cholesterol inhibits formation of several polyprenyl derivatives involved in signal transduction. In the present study, we examined whether PC and cardiac NO synthesis are restored by treatment with the key polyprenyl product, farnesol, in cholesterol-fed rats. Rats fed 2% cholesterol-enriched/control diet for 24 weeks were given i.p. 5 μM/kg farnesol/vehicle, respectively. An hour later, hearts were isolated and prepared for 'working' perfusion, then subjected to PC/non-PC protocols of 3 intermittent periods of pacing of 5 min duration at 10 Hz, followed by a 10 min coronary occlusion to test the effect of PC. PC increased ischemic aortic flow (AF) from its control value of 15.6 ± 1.5 to 27.3 ± 1.7 mL/min (p <0.05). PC was not observed in hearts obtained from hypercholesterolemic rats (AF: 15.7 ± 1.2 mL/min), however, it reappeared in the farnesol-treated hypercholesterolemic group (AF: 31.8 ± 3.4 mL/min, p <0.05). In tissue samples from the left ventricle, cholesterol-diet markedly decreased the intensity of the electron spin resonance spectra of NO obtained after in vivo spin trapping with Fe2+-diethyl-dithio-carbamate complex. Farnesol-treatment did not influence cardiac NO content in the cholesterol-fed or in the control group. These results show that the lost PC can be recaptured by farnesol-treatment in hypercholesterolemia, however, farnesol-treatment does not restore cardiac NO synthesis.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume186
Issue number1-2
DOIs
Publication statusPublished - 1998

Fingerprint

Farnesol
Rats
Nitric Oxide
Cholesterol
Derivatives
Nutrition
Hypercholesterolemia
Therapeutics
Diet
Spin Trapping
Ischemic Preconditioning
Signal transduction
Carbamates
Coronary Occlusion
Electron Spin Resonance Spectroscopy
Heart Ventricles
Paramagnetic resonance
Signal Transduction
Perfusion
Tissue

Keywords

  • Electron spin resonance
  • Farnesol
  • High-cholesterol diet
  • Nitric oxide
  • Pacing
  • Preconditioning
  • Rat heart

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

@article{c0b94957ae83406486d7428dfe7a4266,
title = "Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol fed rats: Role of polyprenyl derivatives and nitric oxide",
abstract = "We have previously shown that hypercholesterolemia leads to the loss of pacing-induced preconditioning (PC), possibly due to the impairment of cardiac nitric oxide (NO) synthesis. It has been shown that excess exogenous cholesterol inhibits formation of several polyprenyl derivatives involved in signal transduction. In the present study, we examined whether PC and cardiac NO synthesis are restored by treatment with the key polyprenyl product, farnesol, in cholesterol-fed rats. Rats fed 2{\%} cholesterol-enriched/control diet for 24 weeks were given i.p. 5 μM/kg farnesol/vehicle, respectively. An hour later, hearts were isolated and prepared for 'working' perfusion, then subjected to PC/non-PC protocols of 3 intermittent periods of pacing of 5 min duration at 10 Hz, followed by a 10 min coronary occlusion to test the effect of PC. PC increased ischemic aortic flow (AF) from its control value of 15.6 ± 1.5 to 27.3 ± 1.7 mL/min (p <0.05). PC was not observed in hearts obtained from hypercholesterolemic rats (AF: 15.7 ± 1.2 mL/min), however, it reappeared in the farnesol-treated hypercholesterolemic group (AF: 31.8 ± 3.4 mL/min, p <0.05). In tissue samples from the left ventricle, cholesterol-diet markedly decreased the intensity of the electron spin resonance spectra of NO obtained after in vivo spin trapping with Fe2+-diethyl-dithio-carbamate complex. Farnesol-treatment did not influence cardiac NO content in the cholesterol-fed or in the control group. These results show that the lost PC can be recaptured by farnesol-treatment in hypercholesterolemia, however, farnesol-treatment does not restore cardiac NO synthesis.",
keywords = "Electron spin resonance, Farnesol, High-cholesterol diet, Nitric oxide, Pacing, Preconditioning, Rat heart",
author = "P. Ferdin{\'a}ndy and C. Csonka and T. Csont and Z. Szilv{\'a}ssy and L. Dux",
year = "1998",
doi = "10.1023/A:1006832929044",
language = "English",
volume = "186",
pages = "27--34",
journal = "Molecular and Cellular Biochemistry",
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T1 - Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol fed rats

T2 - Role of polyprenyl derivatives and nitric oxide

AU - Ferdinándy, P.

AU - Csonka, C.

AU - Csont, T.

AU - Szilvássy, Z.

AU - Dux, L.

PY - 1998

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N2 - We have previously shown that hypercholesterolemia leads to the loss of pacing-induced preconditioning (PC), possibly due to the impairment of cardiac nitric oxide (NO) synthesis. It has been shown that excess exogenous cholesterol inhibits formation of several polyprenyl derivatives involved in signal transduction. In the present study, we examined whether PC and cardiac NO synthesis are restored by treatment with the key polyprenyl product, farnesol, in cholesterol-fed rats. Rats fed 2% cholesterol-enriched/control diet for 24 weeks were given i.p. 5 μM/kg farnesol/vehicle, respectively. An hour later, hearts were isolated and prepared for 'working' perfusion, then subjected to PC/non-PC protocols of 3 intermittent periods of pacing of 5 min duration at 10 Hz, followed by a 10 min coronary occlusion to test the effect of PC. PC increased ischemic aortic flow (AF) from its control value of 15.6 ± 1.5 to 27.3 ± 1.7 mL/min (p <0.05). PC was not observed in hearts obtained from hypercholesterolemic rats (AF: 15.7 ± 1.2 mL/min), however, it reappeared in the farnesol-treated hypercholesterolemic group (AF: 31.8 ± 3.4 mL/min, p <0.05). In tissue samples from the left ventricle, cholesterol-diet markedly decreased the intensity of the electron spin resonance spectra of NO obtained after in vivo spin trapping with Fe2+-diethyl-dithio-carbamate complex. Farnesol-treatment did not influence cardiac NO content in the cholesterol-fed or in the control group. These results show that the lost PC can be recaptured by farnesol-treatment in hypercholesterolemia, however, farnesol-treatment does not restore cardiac NO synthesis.

AB - We have previously shown that hypercholesterolemia leads to the loss of pacing-induced preconditioning (PC), possibly due to the impairment of cardiac nitric oxide (NO) synthesis. It has been shown that excess exogenous cholesterol inhibits formation of several polyprenyl derivatives involved in signal transduction. In the present study, we examined whether PC and cardiac NO synthesis are restored by treatment with the key polyprenyl product, farnesol, in cholesterol-fed rats. Rats fed 2% cholesterol-enriched/control diet for 24 weeks were given i.p. 5 μM/kg farnesol/vehicle, respectively. An hour later, hearts were isolated and prepared for 'working' perfusion, then subjected to PC/non-PC protocols of 3 intermittent periods of pacing of 5 min duration at 10 Hz, followed by a 10 min coronary occlusion to test the effect of PC. PC increased ischemic aortic flow (AF) from its control value of 15.6 ± 1.5 to 27.3 ± 1.7 mL/min (p <0.05). PC was not observed in hearts obtained from hypercholesterolemic rats (AF: 15.7 ± 1.2 mL/min), however, it reappeared in the farnesol-treated hypercholesterolemic group (AF: 31.8 ± 3.4 mL/min, p <0.05). In tissue samples from the left ventricle, cholesterol-diet markedly decreased the intensity of the electron spin resonance spectra of NO obtained after in vivo spin trapping with Fe2+-diethyl-dithio-carbamate complex. Farnesol-treatment did not influence cardiac NO content in the cholesterol-fed or in the control group. These results show that the lost PC can be recaptured by farnesol-treatment in hypercholesterolemia, however, farnesol-treatment does not restore cardiac NO synthesis.

KW - Electron spin resonance

KW - Farnesol

KW - High-cholesterol diet

KW - Nitric oxide

KW - Pacing

KW - Preconditioning

KW - Rat heart

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