Cardiology

Effect of chronic continuous normobaric hypoxia on functional state of cardiac mitochondria and tolerance of isolated rat heart to ischemia and reperfusion: role of µ and delta2 opioid receptors.

Effect of chronic continuous normobaric hypoxia on functional state of cardiac mitochondria and tolerance of isolated rat heart to ischemia and reperfusion: role of µ and delta2 opioid receptors.

Physiol Res. 2019 Oct 25;

Authors: Prokudina ES, Naryzhnaya NV, Mukhomedzyanov AV, Gorbunov AS, Zhang Y, Jaggi AS, Tsibulnikov SY, Nesterov EA, Lishmanov YB, Suleiman MS, Oeltgen PR, Maslov LN

Abstract
Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and delta2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and delta2 ORs and preservation of mitochondrial function. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective delta OR antagonist TIPP(psi) (30 nmol/l), the selective delta1 OR antagonist BNTX (1 nmol/l), the selective delta2 OR antagonist naltriben (1 nmol/l), the selective peptide delta OR antagonist CTAP (100 nmol/l) and the selective kappa OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(psi), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and delta2 opioid receptors activation and preservation of mitochondrial function.

PMID: 31647288 [PubMed – as supplied by publisher]

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