beta-Adrenergic signaling, monoamine oxidase A and antioxidant defence in the myocardium of SHR and SHR-mtBN conplastic rat strains: the effect of chronic hypoxia

0490865 - FGÚ 2019 RIV JP eng J - Článek v odborném periodiku
Hahnová, K. - Brabcová, I. - Neckář, Jan - Weissová, Romana - Svatoňová, Anna - Nováková, O. - Žurmanová, J. - Kalous, M. - Šilhavý, Jan - Pravenec, Michal - Kolář, František - Novotný, J.
beta-Adrenergic signaling, monoamine oxidase A and antioxidant defence in the myocardium of SHR and SHR-mtBN conplastic rat strains: the effect of chronic hypoxia.
Journal of Physiological Sciences. Roč. 68, č. 4 (2018), s. 441-454. ISSN 1880-6546. E-ISSN 1880-6562
Grant CEP: GA ČR(CZ) GA13-10267S; GA MŠMT(CZ) LL1204; GA ČR(CZ) GAP301/12/0696
Institucionální podpora: RVO:67985823
Klíčová slova: SHR * mitochondrial genome * myocardium * beta-adrenergic receptors * adenylyl cyclase * monoamine oxidase A * antioxidant defence * chronic hypoxia
Obor OECD: Physiology (including cytology)
Impakt faktor: 3.341, rok: 2018

The beta-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% O-2, 3 weeks) on myocardial beta-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 beta-adrenergic receptors (beta-ARs), activity of adenylyl cyclase (AC) and monoamine oxidase A (MAO-A), as well as distinct changes after CNH exposure. The beta(2)-AR/beta(1)-AR ratio was significantly higher in SHR-mtBN than in SHR, apparently due to increased expression of beta(2)-ARs. Adaptation to hypoxia elevated beta(2)-ARs in SHR and decreased the total number of beta-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-alpha ratio in SHR-mtBN only. These data indicate that alterations in the mitochondrial genome can result in peculiar changes in myocardial beta-adrenergic signaling, MAO-A activity and antioxidant defence and may, thus, affect the adaptive responses to hypoxia.
Trvalý link: http://hdl.handle.net/11104/0284995