Long-term postinfarction melatonin administration alters the expression of DHPR, RyR2, SERCA2, and MT2 and elevates the ANP level in the rat left ventricle.
We investigated the effect of 2 wk continuous postinfarction subcutaneous melatonin supply on the expression of the rat left ventricular (LV) dihydropyridine receptor (DHPR), ryanodine receptor (RyR(2)), and sarco-endoplasmic reticulum Ca(2+)-ATPase2 (SERCA2), as they are fundamental proteins in cardiac contractility. The levels of plasma and LV atrial (ANP) and brain natriuretic peptide and melatonin were also measured, as was the expression of LV MT(1) and MT(2) receptors and pineal arylalkylamine N-acetyltransferase. Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery and vehicle or melatonin (4.5 mg/kg per day) was administered by subcutaneous osmotic pumps. Echocardiography, real-time quantitative reverse transcription-polymerase chain reaction, and western blotting were used to analyze the samples. Echocardiography revealed that MI induced serious systolic LV dysfunction. The expression of DHPR, RyR(2), and SERCA2 mRNAs was significantly lower in the LVs of melatonin-treated MI rats compared with vehicle-treated rats (P < 0.01 for DHPR and P < 0.05 for RyR(2) and SERCA2). Melatonin also elevated the amount of LV MT(2) receptors to 1.9-fold (P < 0.05) and the concentration of LV ANP to over fivefold (P < 0.05) compared with vehicle rats after MI. Therefore, the results suggest that melatonin may influence the cardiac contractility after MI by regulating the expression of DHPR, RyR(2), and SERCA2, and melatonin receptors, particularly MT(2)s, might contribute to the postinfarction cardioprotective actions of melatonin. Furthermore, the finding of the relationship between melatonin and ANP suggests a novel mechanism for melatonin in protecting the heart after MI.
Sallinen
Pirkko
P
Department of Biology, University of Oulu, Oulu, Finland. pirkko.sallinen@oulu.fi
Mänttäri
Satu
S
Leskinen
Hanna
H
Vakkuri
Olli
O
Ruskoaho
Heikki
H
Saarela
Seppo
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044123:Receptor, Melatonin, MT2 / Q000096:biosynthesis* / Q000235:genetics; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis* / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics
C506948:Atp2a2 protein, rat; D020746:Calcium Channels, L-Type; D044123:Receptor, Melatonin, MT2; D019837:Ryanodine Receptor Calcium Release Channel; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D008550:Melatonin