Growth hormone secretagogues protect mouse cardiomyocytes from in vitro ischemia/reperfusion injury through regulation of intracellular calcium.

Ma Y, Zhang L, Edwards JN, Launikonis BS, Chen C

PloS one6 Apr 2012Cited by 31 (Europe PMC)

PMID22493744PMCIDPMC3320867DOI10.1371/journal.pone.0035265PepBankPUB-22493744

Summary

BackgroundIschemic heart disease is a leading cause of mortality. To study this disease, ischemia/reperfusion (I/R) models are widely used to mimic the process of transient blockage and subsequent recovery of cardiac coronary blood supply. We aimed to determine whether the presence of the growth hormone secretagogues, ghrelin and hexarelin, would protect/improve the function of heart from I/R injury and to examine the underlying mechanisms.Methodology/principal findingsIsolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus. Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments. In freshly isolated cardiomyocytes from these hearts, single cell shortening, intracellular calcium ([Ca(2+)](i)) transients and caffeine-releasable sarcoplasmic reticulum (SR) Ca(2+) were measured. In addition, RT-PCR and Western blots were used to examine the expression level of GHS receptor type 1a (GHS-R1a), and phosphorylated phospholamban (p-PLB), respectively. Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+)](i) transient amplitude and caffeine-releasable SR Ca(2+) content after I/R through recovery of p-PLB. GHS-R1a antagonists, [D-Lys3]-GHRP-6 (200 nM) and BIM28163 (100 nM), completely blocked the effects of GHS on both cell shortening and [Ca(2+)](i) transients.Conclusion/significanceThrough activation of GHS-R1a, ghrelin and hexarelin produced a positive inotropic effect on ischemic cardiomyocytes and protected them from I/R injury probably by protecting or recovering p-PLB (and therefore SR Ca(2+) content) to allow the maintenance or recovery of normal cardiac contractility. These observations provide supporting evidence for the potential therapeutic application of ghrelin and hexarelin in patients with cardiac I/R injury.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

4 results from studies that gave the peptide. No result from this study comes from people.

01LabEx vivo tissueEfficacy outcome
In mouse cardiomyocytes from hearts with ischemia/reperfusion injury, hexarelin pre- or post-treatment prevented the significant reduction in cell shortening.
In plain wordsIn cells from mouse hearts, hexarelin given before or after blocked blood flow prevented the loss of cell contraction.
Peptide
Hexarelin
Outcome
IncreaseCardiomyocyte cell shortening after I/R
Study
mousen: not reported in source
Langendorff-perfused mouse hearts and isolated cardiomyocytes after ischemia/reperfusion
Outcome group
Heart function · Cardiovascular
Studied dose
1 nM · perfusionAs given in this study (mouse).
Source sentences
Summary
Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+)](i) transient amplitude and caffeine-releasable SR Ca(2+) content after I/R through recovery of p-PLB.
2 context sentences(design, population, supporting numbers)
Summary · context
Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus.
Summary · context
Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments.
Show in the study text Report a problemFND-2249374401
02LabEx vivo tissueEfficacy outcome
In mouse cardiomyocytes from hearts with ischemia/reperfusion injury, hexarelin pre- or post-treatment prevented the significant reduction in calcium transient amplitude.
In plain wordsIn cells from mouse hearts, hexarelin given before or after blocked blood flow prevented the fall in calcium signals.
Peptide
Hexarelin
Outcome
IncreaseCalcium transient amplitude after I/R
Study
mousen: not reported in source
Langendorff-perfused mouse hearts and isolated cardiomyocytes after ischemia/reperfusion
Outcome group
Heart function · Cardiovascular
Studied dose
1 nM · perfusionAs given in this study (mouse).
Source sentences
Summary
Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+)](i) transient amplitude and caffeine-releasable SR Ca(2+) content after I/R through recovery of p-PLB.
2 context sentences(design, population, supporting numbers)
Summary · context
Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus.
Summary · context
Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments.
Show in the study text Report a problemFND-2249374402
03LabEx vivo tissueEfficacy outcome
In mouse cardiomyocytes from hearts with ischemia/reperfusion injury, hexarelin pre- or post-treatment prevented the significant reduction in caffeine-releasable sarcoplasmic reticulum calcium content.
In plain wordsIn cells from mouse hearts, hexarelin given before or after blocked blood flow prevented the fall in stored calcium.
Peptide
Hexarelin
Outcome
IncreaseCaffeine-releasable SR calcium content after I/R
Study
mousen: not reported in source
Langendorff-perfused mouse hearts and isolated cardiomyocytes after ischemia/reperfusion
Outcome group
Heart function · Cardiovascular
Studied dose
1 nM · perfusionAs given in this study (mouse).
Source sentences
Summary
Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+)](i) transient amplitude and caffeine-releasable SR Ca(2+) content after I/R through recovery of p-PLB.
2 context sentences(design, population, supporting numbers)
Summary · context
Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus.
Summary · context
Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments.
Show in the study text Report a problemFND-2249374403
04LabEx vivo tissueMechanism
In mouse cardiomyocytes after ischemia/reperfusion, the protective effects of hexarelin were linked to recovery of phosphorylated phospholamban.
In plain wordsIn cells from mouse hearts, hexarelin's protective effects were linked to recovery of phosphorylated phospholamban.
Peptide
Hexarelin
Outcome
IncreasePhosphorylated phospholamban recovery
Study
mousen: not reported in source
Langendorff-perfused mouse hearts and isolated cardiomyocytes after ischemia/reperfusion
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
1 nM · perfusionAs given in this study (mouse).
Source sentences
Summary
Ghrelin and hexarelin pre- or post-treatments prevented the significant reduction in the cell shortening, [Ca(2+)](i) transient amplitude and caffeine-releasable SR Ca(2+) content after I/R through recovery of p-PLB.
2 context sentences(design, population, supporting numbers)
Summary · context
Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus.
Summary · context
Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments.
Show in the study text Report a problemFND-2249374404

Studies that did not test the peptide alone1

In this study, Hexarelin was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Hexarelin.

05LabNot a test of Hexarelin aloneEx vivo tissueMechanism
In mouse cardiomyocytes, the GHS-R1a antagonists [D-Lys3]-GHRP-6 and BIM28163 completely blocked the effects of the secretagogues on cell shortening and calcium transients.
In plain wordsIn cells from mouse hearts, two receptor blockers completely stopped the effects of the secretagogues on cell contraction and calcium signals.
Peptide
Hexarelin
Outcome
Not applicableEffect of GHS-R1a antagonists on cell shortening and calcium transients
Study
mousen: not reported in source
Langendorff-perfused mouse hearts and isolated cardiomyocytes after ischemia/reperfusion
Outcome group
Receptor activity and mechanism · Cardiovascular
Source sentences
Summary
GHS-R1a antagonists, [D-Lys3]-GHRP-6 (200 nM) and BIM28163 (100 nM), completely blocked the effects of GHS on both cell shortening and [Ca(2+)](i) transients.
2 context sentences(design, population, supporting numbers)
Summary · context
Isolated hearts from adult male mice underwent 20 min global ischemia and 30 min reperfusion using a Langendorff apparatus.
Summary · context
Ghrelin (10 nM) or hexarelin (1 nM) was introduced into the perfusion system either 10 min before or after ischemia, termed pre- and post-treatments.
In this study, Hexarelin was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Hexarelin.
Show in the study text Report a problemFND-2249374405

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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