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

53 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number4 56-4
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

Fingerprint

Ghrelin
Vasoconstriction
Peptides
Diltiazem
Arterioles
Atrial Natriuretic Factor
Cardiac Myocytes
Protein Kinase C
Gene Expression
Pressure
Growth Hormone-Releasing Hormone
Natriuretic Peptides
Tissue Extracts
Protein C Inhibitor
Brain Natriuretic Peptide
Vasoconstrictor Agents
Protein Kinase Inhibitors
Blood Vessels
Perfusion
Molecular Weight

Keywords

  • Calcium channels
  • Natriuretic peptides
  • Protein kinases

ASJC Scopus subject areas

  • Physiology

Cite this

Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion. / Pemberton, Chris J.; Tokola, Heikki; Bagi, Zsolt; Koller, Akos; Pöntinen, Juhani; Ola, Antti; Vuolteenaho, Olli; Szokodi, István; Ruskoaho, Heikki.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 287, No. 4 56-4, 01.10.2004.

Research output: Contribution to journalArticle

Pemberton, Chris J. ; Tokola, Heikki ; Bagi, Zsolt ; Koller, Akos ; Pöntinen, Juhani ; Ola, Antti ; Vuolteenaho, Olli ; Szokodi, István ; Ruskoaho, Heikki. / Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion. In: American Journal of Physiology - Heart and Circulatory Physiology. 2004 ; Vol. 287, No. 4 56-4.
@article{cfcfe216e370483fbf67b926438b1fea,
title = "Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion",
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.",
keywords = "Calcium channels, Natriuretic peptides, Protein kinases",
author = "Pemberton, {Chris J.} and Heikki Tokola and Zsolt Bagi and Akos Koller and Juhani P{\"o}ntinen and Antti Ola and Olli Vuolteenaho and Istv{\'a}n Szokodi and Heikki Ruskoaho",
year = "2004",
month = "10",
day = "1",
doi = "10.1152/ajpheart.00193.2004",
language = "English (US)",
volume = "287",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 56-4",

}

TY - JOUR

T1 - Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion

AU - Pemberton, Chris J.

AU - Tokola, Heikki

AU - Bagi, Zsolt

AU - Koller, Akos

AU - Pöntinen, Juhani

AU - Ola, Antti

AU - Vuolteenaho, Olli

AU - Szokodi, István

AU - Ruskoaho, Heikki

PY - 2004/10/1

Y1 - 2004/10/1

N2 - 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.

AB - 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.

KW - Calcium channels

KW - Natriuretic peptides

KW - Protein kinases

UR - http://www.scopus.com/inward/record.url?scp=4744343651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4744343651&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00193.2004

DO - 10.1152/ajpheart.00193.2004

M3 - Article

VL - 287

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 56-4

ER -