Cardioprotective Effect of 3-Iodothyronamine in Perfused Rat Heart Subjected to Ischemia and Reperfusion
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Sabina Frascarelli , Sandra Ghelardoni , Grazia Chiellini , Elena Galli , Francesca Ronca , Thomas S. Scanlan , Riccardo Zucchi
- چاپ و سال / کشور: 2011
Description
3-iodothyronamine (T1AM) is an endogenous compound which shares structural and functional features with biogenic amines and is able to interact with a specific class of receptors, designed as trace amine associated receptors. T1AM has significant physiological effects in mammals and produces a reversible, dose-dependent negative inotropic and chronotropic effect in heart. The aim of the present study was to investigate if T1AM is able to reduce irreversible tissue injury in isolated rat hearts subjected to ischemia and reperfusion, as evaluated by triphenyltetrazolium chloride staining. We observed that T1AM reduced infarct size at concentrations (125 nM to 12.5 ىM) which did not produce any significant hemodynamic action. The dose–response curve was bell-shaped and peaked at 1.25 ىM. T1AM-induced cardioprotection was completely reversed by the administration of chelerythrine and glibenclamide, suggesting a protein kinase C and KATP +-dependent pathway, while it was not additive to the protection induced by cyclosporine A, suggesting modulation of mitochondrial permeability transition. At cardioprotective concentration, T1AM reduced the time needed for cardiac attest during ischemia, but it did not affect sarcoplasmatic reticulum Ca2+ handling, as demonstrated by unaltered ryanodine receptor binding properties. In conclusion, in isolated rat heart T1AM produces a cardioprotective effect which is mediated by a protein kinase C and KATP +-dependent pathway and is probably linked to modulation of mitochondrial permeability transition and/or ischemic arrest time.
Cardiovasc Drugs Ther (2011) 25:307–313 Published online: 26 July 201
