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On the participation of adenosine and cannabinoid receptors in the infarct‐limiting effect of chronic normobaric hypoxia
Author(s) -
Naryzhnaya Natalia,
Derkachev Ivan,
Krylatov Andrey,
Maslov Leonid
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05022
Subject(s) - cannabinoid , cannabinoid receptor , medicine , antagonist , adenosine receptor , hypoxia (environmental) , pharmacology , adenosine , anesthesia , agonist , receptor , chemistry , organic chemistry , oxygen
It is known that moderate chronic hypoxia leads to an increase in myocardial resistance to ischemia‐reperfusion. The receptor mechanisms of this phenomenon are poorly understood. The aim of the study was to identify the participation of adenosine and cannabinoid receptors in the infarction‐limiting effect of chronic normobaric hypoxia. The experiments were carried out on male Wistar rats weighing 250–300 g. All procedures conformed to the Directive 2010/63/EU of the European Parliament and FASEB Statement of Principles for the use of Animals in Research and Education. Ethical approval was granted by the Ethical Committee of Research Institute of Cardiology, Tomsk National Research Medical Center. The animals were randomly divided into 8 groups, 12 animals in each. Control rats were kept in standard normoxic conditions. The animals of the experimental groups were exposed to chronic continuous normobaric hypoxia ( CNH ) in the hypoxic chamber for 21 days at the concentrations of O 2 (12%) and CO 2 (0.3%) inside the hypoxic chamber at the temperature of 23±1°C and at the normal atmospheric pressure. A day after completion of CNH it was performed coronary artery occlusion (45 min) and reperfusion (2 h). In a study the following compounds were used: antagonist of all type of adenosine receptor 8‐p‐(sulfophenyl) theophylline (7.5 mg/kg); the selective cannabinoid CB1 receptor antagonist rimonabant (1 mg/kg); the selective cannabinoid CB2 receptor antagonist AM630 (2.5 mg/kg). All antagonists were administered 15 min before coronary artery occlusion. Adaptation to normobaric hypoxia promoted the formation of the pronounced infarct‐limiting effect: infarct size in this group was 34% of area at risk vs 54% in control group. No one of adenosine or cannabinoid receptor antagonists affected the infarct size in control rats. Blockade of adenosine receptors in rats exposed to CNH eliminate infarct‐limiting effect of CNH. Blockade of cannabinoid CB1 ore CB2‐receptors did not affect the infarct‐limiting effect of CNH. Consequently, the infarct‐limiting effect of CNH depends on activation of adenosine receptor, and an adaptive increase in cardiac tolerance to ischemia/reperfusion does not depend on cannabinoid receptors.