Both
hexarelin and its natural analog
ghrelin exert comparable cardioprotective activities. A single dose of
ghrelin administered at the very acute phase after experimental
myocardial infarction positively affects cardiac function in chronic
heart failure. Therefore, this study aimed to determine whether a single dose of oral
hexarelin has the same effect in the
chronic disease phase.
Myocardial infarction or
sham operation was generated by left coronary artery
ligation in male C57BL/6J mice, which subsequently received one dose of
hexarelin or vehicle treatment by oral gavage 30 min after operation. Although the mortality within 14 days after
myocardial infarction did not differ between the groups,
hexarelin treatment protected cardiac function in the chronic phase as evidenced by higher ejection fraction and fractional shortening, as well as lower lung
weight/body weight and lung weight/tibial length ratios, compared with vehicle treatment.
Hexarelin treatment concurrently lowered plasma
epinephrine and
dopamine levels, and shifted the balance of autonomic nervous activity toward parasympathetic nervous activity as evidenced by a smaller low/high-frequency power ratio and larger normalized high-frequency power on heart rate variability analysis. The results first demonstrate that one dose of oral
hexarelin treatment potentially protects chronic cardiac function after acute
myocardial infarction, and implicate that activating
growth hormone secretagogue receptor 1a might be beneficial for cardioprotection, although other mechanism may also be involved.