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Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol-fed rats: Role of polyprenyl derivatives and nitric oxide

Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biochemistry Springer Journals

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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References (53)

Publisher
Springer Journals
Copyright
Copyright © 1998 by Kluwer Academic Publishers
Subject
Life Sciences; Cardiology; Medical Biochemistry; Oncology; Biochemistry, general
ISSN
0300-8177
eISSN
1573-4919
DOI
10.1023/A:1006832929044
Publisher site
See Article on Publisher Site

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.

Journal

Molecular and Cellular Biochemistry – Springer Journals

Published: Oct 4, 2004

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