Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion

Chris J. Pemberton, Heikki Tokola, Zsolt Bagi, Akos Koller, Juhani Pöntinen, Antti Ola, Olli Vuolteenaho, István Szokodi, Heikki Ruskoaho

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

We administered ghrelin, a novel growth hormone-releasing hormone, to isolated perfused rat hearts, coronary arterioles, and cultured neonatal cardiomyocytes to determine its effects on coronary vascular tone, contractility, and natriuretic peptide secretion and gene expression. We also determined cardiac levels of ghrelin and whether the heart is a source of the circulating peptide. Ghrelin dose dependently increased coronary perfusion pressure (44 ± 9%, P < 0.01), constricted isolated coronary arterioles (12 ± 2%, P < 0.05), and significantly enhanced the pressure-induced myogenic tone of arterioles. These effects were blocked by diltiazem, an L-type Ca2+ channel blocker, and bisindolylmaleimide (Bis), a protein kinase C (PKC) inhibitor. Interestingly, coinfusion of ghrelin with diltiazem completely restored myocardial contractile function that was decreased 30 ± 3% (P < 0.01) by diltiazem alone. In contrast, combination of ghrelin with diltiazem or Bis did not significantly alter atrial natriuretic peptide (ANP) secretion, which was decreased 40% (P < 0.01) and 50% (P < 0.05) by these agents alone, respectively. Administration of ghrelin to cultured cardiomyocytes had no effect on ANP or B-type natriuretic peptide secretion or gene expression. Detectable amounts of low-molecular-weight ghrelin were present in cardiac tissue extracts but not in isolated heart perfusate. Thus we provide the first evidence that ghrelin has a coronary vasoconstrictor action that is dependent on Ca2+ and PKC. Furthermore, the data obtained from diltiazem infusion suggest that ghrelin has a role in regulation of contractility when L-type Ca2+ channels are blocked. Finally, the observation that immunoreactive ghrelin is found in cardiac tissue suggests the presence of a local cardiac ghrelin system.

Original languageEnglish (US)
Pages (from-to)H1522-H1529
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

Keywords

  • Calcium channels
  • Natriuretic peptides
  • Protein kinases

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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