Role of cholesterol-enriched diet and the mevalonate pathway in cardiac nitric oxide synthesis

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cardiac stress adaptation is deteriorated in hyperlipidemia possibly due to deterioration of nitric oxide (NO) metabolism. However, inhibition of HMG-CoA reductase, a key enzyme in the mevalonate pathway, was shown to increase the level of endothelial NO-synthase (eNOS) mRNA. Here we studied the effect of dietary and pharmacologic modulation of the mevalonate pathway on cardiac NO synthesis. Rats were fed 2 % cholesterol-enriched or normal diet for 8 weeks. Normal and cholesterol-fed animals were treated with farnesol, a major metabolite of the mevalonate pathway (2.2 mg/kg i.p.) or with the HMG-CoA reductase inhibitor lovastatin (3 × 5 mg/kg per os for 3 days, n = 5-6 in each group). Cardiac NO content was significantly decreased in cholesterol-fed rats as assessed by electron spin resonance spectroscopy, however, other treatments did not influence cardiac NO content. Cardiac activity of Ca2+-dependent NOS was unaffected by cholesterol-diet and by treatment with either farnesol or lovastatin, as assessed by 14C-citrullin assay. Ca2+-independent NOS activity was negligible in all groups. Cardiac eNOS protein content measured by Western blotting was also unchanged in all groups. We conclude that cholesterol-diet decreases cardiac NO content, however, cholesterol diet-induced inhibition of the mevalonate pathway does not account for the decreased NO level in the heart, and that the mevalonate pathway does not influence cardiac NO biosynthesis.

Original languageEnglish
Pages (from-to)304-310
Number of pages7
JournalBasic Research in Cardiology
Volume98
Issue number5
DOIs
Publication statusPublished - Sep 2003

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Mevalonic Acid
Nitric Oxide
Cholesterol
Diet
Farnesol
Lovastatin
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide Synthase Type III
Electron Spin Resonance Spectroscopy
Hyperlipidemias
Nitric Oxide Synthase
Western Blotting
Messenger RNA
Enzymes

Keywords

  • Heart
  • Hyperlipidemia
  • Mevalonate pathway
  • Nitric oxide
  • Superoxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Role of cholesterol-enriched diet and the mevalonate pathway in cardiac nitric oxide synthesis. / Giricz, Z.; Csonka, C.; Ónody, Annamária; Csont, T.; Ferdinándy, P.

In: Basic Research in Cardiology, Vol. 98, No. 5, 09.2003, p. 304-310.

Research output: Contribution to journalArticle

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