Deterioration of the protein kinase C-KATP channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits

Eva Pongo, Zsolt Balla, Kanigula Mubagwa, Willem Flameng, I. Édes, Z. Szilvássy, P. Ferdinándy

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We studied the effect of experimental hypercholesterolaemia/atherosclerosis on changes in coronary flow and cardiac function, induced by protein kinase C and ATP-sensitive K+ (KATP) channel modulators in isolated Langendorff-perfused rabbit hearts. Both phorbol 12-myristate-13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB, 0.1 μM each), activators of protein kinase C, decreased, whereas staurosporine, (0.1 μM), a protein kinase C inhibitor, increased coronary flow and left ventricular dP/dt, an index of ventricular contractility. Glyburide (5-50 μM), a KATP channel inhibitor, blocked the effect of staurosporine. The phorbol esters were without effect in the presence of pinacidil (5 μM), a KATP channel activator. Neither the protein kinase C modulators nor glyburide produced any effect on coronary flow and left ventricular contractility, when the hearts were prepared from animals either maintained on a cholesterol (1.5%)-enriched diet or treated with lovastatin (5 mg/kg/day per os). Treatment with farnesol (1 mg/kg twice a day for 7 days intravenously) restored the reactivity of hearts from either hypercholesterolaemic or lovastatin-treated animals to protein kinase C modulators. We conclude that non-cholesterol mevalonate products are necessary for the functional integrity of the protein kinase C-KATP channel pathway in the rabbit heart.

Original languageEnglish
Pages (from-to)217-223
Number of pages7
JournalEuropean Journal of Pharmacology
Volume418
Issue number3
DOIs
Publication statusPublished - Apr 27 2001

Fingerprint

KATP Channels
Protein Kinase C
Rabbits
Lovastatin
Staurosporine
Glyburide
Farnesol
Pinacidil
Phorbol 12,13-Dibutyrate
Myocardial Contraction
Mevalonic Acid
Protein C Inhibitor
Phorbol Esters
Protein Kinase Inhibitors
Hypercholesterolemia
Atherosclerosis
Acetates
Adenosine Triphosphate
Cholesterol
Diet

Keywords

  • Farnesol
  • Heart
  • Hypercholesterolaemia
  • K channel
  • Protein kinase C
  • Rabbit

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Deterioration of the protein kinase C-KATP channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits. / Pongo, Eva; Balla, Zsolt; Mubagwa, Kanigula; Flameng, Willem; Édes, I.; Szilvássy, Z.; Ferdinándy, P.

In: European Journal of Pharmacology, Vol. 418, No. 3, 27.04.2001, p. 217-223.

Research output: Contribution to journalArticle

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