ORIGINAL PAPER
b-Adrenergic signaling, monoamine oxidase A and antioxidant
defence in the myocardium of SHR and SHR-mtBN conplastic rat
strains: the effect of chronic hypoxia
Klara Hahnova
1
•
Iveta Brabcova
1
•
Jan Neckar
2
•
Romana Weissova
2
•
Anna Svatonova
2
•
Olga Novakova
1
•
Jitka Zurmanova
1
•
Martin Kalous
3
•
Jan Silhavy
2
•
Michal Pravenec
2
•
Frantisek Kolar
2
•
Jiri Novotny
1
Received: 8 February 2017 / Accepted: 23 May 2017 / Published online: 31 May 2017
Ó The Physiological Society of Japan and Springer Japan 2017
Abstract The b-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 b-adrenergic signaling and selec-
ted 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 investiga-
tions revealed some intriguing differences between the two
strains at the level of b-adrenergic receptors (b-ARs),
activity of adenylyl cyclase (AC) and monoamine oxidase
A (MAO-A), as well as distinct changes after CNH expo-
sure. The b
2
-AR/b
1
-AR ratio was significantly higher in
SHR-mtBN than in SHR, apparently due to increased
expression of b
2
-ARs. Adaptation to hypoxia elevated b
2
-
ARs in SHR and decreased the total number of b-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 inten-
sified oxidative stress to a similar extent in both strains and
elevated the IL-10/TNF-a ratio in SHR-mtBN only. These
data indicate that alterations in the mitochondrial genome
can result in peculiar changes in myocardial b-adrenergic
signaling, MAO-A activity and antioxidant defence and
may, thus, affect the adaptive responses to hypoxia.
Keywords SHR Á Mitochondrial genome Á Myocardium Á
b-adrenergic receptors Á Adenylyl cyclase Á Monoamine
oxidase A Á Antioxidant defence Á Chronic hypoxia
Introduction
The spontaneously hypertensive rat (SHR) is one of the
most commonly used animal models in cardiovascular
research. This strain, which harbors a deletion variant of
the Cd36 gene, is predisposed to the development of
hypertension and cardiac hypertrophy in adulthood [1]. The
hearts of SHR exhibit higher vulnerability to ischemia/
reperfusion (I/R) injury and susceptibility to ventricular
arrhythmias when compared to normotensive rats [2–4].
Interestingly, despite their reduced ischemic tolerance,
ischemic preconditioning was found to provide beneficial
antiarrhythmic effects in these animals [5]. We have pre-
viously documented that transgenic rescue of defective
Cd36 in SHR rat leads to smaller infarct size induced by
coronary artery occlusion [6]. In addition, transgenic SHR-
Cd36 rats were shown to express a higher number of
myocardial b-adrenergic receptors (b-ARs) and displayed
Electronic supplementary material The online version of this
article (doi:10.1007/s12576-017-0546-8) contains supplementary
material, which is available to authorized users.
& Jiri Novotny
jiri.novotny@natur.cuni.cz
1
Department of Physiology, Faculty of Science, Charles
University, Prague, Czech Republic
2
Institute of Physiology, Czech Academy of Sciences, Prague,
Czech Republic
3
Department of Cell Biology, Faculty of Science, Charles
University, Prague, Czech Republic
123
J Physiol Sci (2018) 68:441–454
https://doi.org/10.1007/s12576-017-0546-8
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