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

• Published in: The journal of physiological sciences Vol. 68; no. 4
• Main Authors: Hahnova, Klara, Brabcova, Iveta, Neckar, Jan, Weissova, Romana, Svatonova, Anna, Novakova, Olga, Zurmanova, Jitka, Kalous, Martin, Silhavy, Jan, Pravenec, Michal, Kolar, Frantisek, Novotny, Jiri
• Format: Journal Article
• Language: English
• Published: Springer 31.05.2017
• Subjects: Antioxidants; Ethylenediaminetetraacetic acid; Genomes; Genomics; Heart; Hypertension; Ischemia; Monoamine oxidase; Superoxide; Norway
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1007/s12576-017-0546-8

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.sub.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].sub.2-AR/[beta].sub.1-AR ratio was significantly higher in SHR-mtBN than in SHR, apparently due to increased expression of [beta].sub.2-ARs. Adaptation to hypoxia elevated [beta].sub.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.