In 2023, six decades have elapsed since the first experimental work on the heart muscle was published, in which a member of the Institute of Physiology of the Czech Academy of Sciences participated as an author; Professor Otakar Poupa was the founder and protagonist of this research domain. Sixty years - more than half of the century - is certainly significant enough anniversary that is worth looking back and reflecting on what was achieved during sometimes very complicated periods of life. It represents the history of an entire generation of experimental cardiologists; it is possible to learn from its successes and mistakes. The objective of this review is to succinctly illuminate the scientific trajectory of an experimental cardiological department over a 60-year span, from its inaugural publication to the present. The old truth - historia magistra vitae - is still valid. Keywords: Heart, Adaptation, Development, Hypoxia, Protection.

• MeSH
• akademie a ústavy * dějiny   MeSH
• biomedicínský výzkum * dějiny   trendy   MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• fyziologie dějiny   MeSH
• kardiologie dějiny   trendy   MeSH
• lidé MeSH
• srdce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

The β-adrenergic signaling pathways and antioxidant defence mechanisms play important roles in maintaining proper heart function. Here, we examined the effect of chronic normobaric hypoxia (CNH, 10% O2, 3 weeks) on myocardial β-adrenergic signaling and selected components of the antioxidant system in spontaneously hypertensive rats (SHR) and in a conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of the more ischemia-resistant Brown Norway strain. Our investigations revealed some intriguing differences between the two strains at the level of β-adrenergic receptors (β-ARs), activity of adenylyl cyclase (AC) and monoamine oxidase A (MAO-A), as well as distinct changes after CNH exposure. The β2-AR/β1-AR ratio was significantly higher in SHR-mtBN than in SHR, apparently due to increased expression of β2-ARs. Adaptation to hypoxia elevated β2-ARs in SHR and decreased the total number of β-ARs in SHR-mtBN. In parallel, the ability of isoprenaline to stimulate AC activity was found to be higher in SHR-mtBN than that in SHR. Interestingly, the activity of MAO-A was notably lower in SHR-mtBN than in SHR, and it was markedly elevated in both strains after exposure to hypoxia. In addition to that, CNH markedly enhanced the expression of catalase and aldehyde dehydrogenase-2 in both strains, and decreased the expression of Cu/Zn superoxide dismutase in SHR. Adaptation to CNH intensified oxidative stress to a similar extent in both strains and elevated the IL-10/TNF-α ratio in SHR-mtBN only. These data indicate that alterations in the mitochondrial genome can result in peculiar changes in myocardial β-adrenergic signaling, MAO-A activity and antioxidant defence and may, thus, affect the adaptive responses to hypoxia.

• Klíčová slova
• Adenylyl cyclase, Antioxidant defence, Chronic hypoxia, Mitochondrial genome, Monoamine oxidase A, Myocardium, SHR, β-adrenergic receptors,
• MeSH
• adenylátcyklasy metabolismus   MeSH
• beta-adrenergní receptory metabolismus   MeSH
• hypoxie metabolismus   MeSH
• krysa rodu Rattus MeSH
• malondialdehyd metabolismus   MeSH
• monoaminoxidasa metabolismus   MeSH
• myokard metabolismus   MeSH
• potkani inbrední SHR MeSH
• signální transdukce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasy MeSH
• beta-adrenergní receptory MeSH
• malondialdehyd MeSH
• monoaminoxidasa MeSH

β-Adrenergic signaling plays an important role in regulating diverse brain functions and alterations in this signaling have been observed in different neuropathological conditions. In this study, we investigated the effect of a 10-day treatment with high doses of morphine (10 mg/kg per day) on major components and functional state of the β-adrenergic receptor (β-AR) signaling system in the rat cerebral cortex. β-ARs were characterized by radioligand binding assays and amounts of various G protein subunits, adenylyl cyclase (AC) isoforms, G protein-coupled receptor kinases (GRKs), and β-arrestin were examined by Western blot analysis. AC activity was determined as a measure of functionality of the signaling system. We also assessed the partitioning of selected signaling proteins between the lipid raft and non-raft fractions prepared from cerebrocortical plasma membranes. Morphine treatment resulted in a significant upregulation of β-ARs, GRK3, and some AC isoforms (AC-I, -II, and -III). There was no change in quantity of G proteins and some other signaling molecules (AC-IV, AC-V/VI, GRK2, GRK5, GRK6, and β-arrestin) compared with controls. Interestingly, morphine exposure caused a partial redistribution of β-ARs, Gsα, Goα, and GRK2 between lipid rafts and bulk plasma membranes. Spatial localization of other signaling molecules within the plasma membrane was not changed. Basal as well as fluoride- and forskolin-stimulated AC activities were not significantly different in membrane preparations from control and morphine-treated animals. However, AC activity stimulated by the beta-AR agonist isoprenaline was markedly increased. This is the first study to demonstrate lipid raft association of key components of the cortical β-AR system and its sensitivity to morphine.

• Klíčová slova
• Adenylyl cyclase, Beta-adrenergic receptors, G proteins, Lipid rafts, Morphine, Rat brain cortex,
• MeSH
• adenylátcyklasy genetika   metabolismus   MeSH
• beta arrestiny genetika   metabolismus   MeSH
• beta-adrenergní receptory metabolismus   MeSH
• kinasa 3 receptorů spřažených s G-proteiny genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• membránové mikrodomény metabolismus   MeSH
• morfin farmakologie   MeSH
• mozková kůra účinky léků   metabolismus   MeSH
• narkotika farmakologie   MeSH
• potkani Wistar MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasy MeSH
• beta arrestiny MeSH
• beta-adrenergní receptory MeSH
• Grk3 protein, rat MeSH Prohlížeč
• kinasa 3 receptorů spřažených s G-proteiny MeSH
• morfin MeSH
• narkotika MeSH

Cardiac resistance against acute ischemia/reperfusion (I/R) injury can be enhanced by adaptation to chronic intermittent hypoxia (CIH), but the changes at the molecular level associated with this adaptation are still not fully explored. Phospholipase A2 (PLA2) plays an important role in phospholipid metabolism and may contribute to membrane destruction under conditions of energy deprivation during I/R. The aim of this study was to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA2α (cPLA2α) and its phosphorylated form (p-cPLA2α), as well as other related signaling proteins in the left ventricular myocardium of adult male Wistar rats. Adaptation to CIH increased the total content of cPLA2α by 14 % in myocardial homogenate, and enhanced the association of p-cPLA2α with the nuclear membrane by 85 %. The total number of β-adrenoceptors (β-ARs) did not change but the β2/β1 ratio markedly increased due to the elevation of β2-ARs and drop in β1-ARs. In parallel, the amount of adenylyl cyclase decreased by 49 % and Giα proteins increased by about 50 %. Besides that, cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) increased by 36 and 84 %, respectively. In parallel, we detected increased phosphorylation of protein kinase Cα, ERK1/2 and p38 (by 12, 48 and 19 %, respectively). These data suggest that adaptive changes induced in the myocardium by CIH may include activation of cPLA2α and COX-2 via β2-AR/Gi-mediated stimulation of the ERK/p38 pathway.

• Klíčová slova
• Cyclooxygenase 2, Heart, Hypoxia, Ischemia/reperfusion, MAPK, Phospholipase A2, β-Adrenoceptor,
• MeSH
• beta-2-adrenergní receptory metabolismus   MeSH
• chronická nemoc MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• fosfolipasy A2, skupina IV metabolismus   MeSH
• ischemická choroba srdeční metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• MAP kinasový signální systém * MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-2-adrenergní receptory MeSH
• cyklooxygenasa 2 MeSH
• fosfolipasy A2, skupina IV MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• Ptgs2 protein, rat MeSH Prohlížeč