1
Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, and Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University and Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, 811 03 Bratislava, Slovakia
3
Heart Biophysics Laboratory, Department of Physiology, Center for Biological and Health Sciences, Federal University of Sergipe, 73330 Sergipe, Brazil
Although -adrenoceptor (-AR) signal transduction,
which maintains cardiac function, is downregulated in failing hearts, the
mechanisms for such a defect in heart failure are not fully understood. Since
cardiac hypertrophy is invariably associated with heart failure, it is possible
that the loss of -AR mechanisms in failing heart occurs due to
hypertrophic process. In this regard, we have reviewed the information from a rat
model of adaptive cardiac hypertrophy and maladaptive hypertrophy at 4 and 24
weeks after inducing pressure overload as well as adaptive cardiac hypertrophy
and heart failure at 4 and 24 weeks after inducing volume overload, respectively.
Varying degrees of alterations in -AR density as well as
isoproterenol-induced increases in cardiac function, intracellular
Ca-concentration in cardiomyocytes and adenylyl cyclase activity in crude
membranes have been reported under these hypertrophic conditions. Adaptive
hypertrophy at 4 weeks of pressure or volume overload showed unaltered or
augmented increases in the activities of different components
of -AR signaling. On the other hand, maladaptive hypertrophy due
to pressure overload and heart failure due to volume overload at 24 weeks
revealed depressions in the activities of -AR signal transduction
pathway. These observations provide evidence that -AR signal
system is either unaltered or upregulated in adaptive cardiac hypertrophy and
downregulated in maladaptive cardiac hypertrophy or heart failure. Furthermore,
the information presented in this article supports the concept that
downregulation of -AR mechanisms in heart failure or maladaptive
cardiac hypertrophy is not due to hypertrophic process per se. It is
suggested that a complex mechanism involving the autonomic imbalance may be of a
critical importance in determining differential alterations in non-failing and
failing hearts.
Naranjan S. Dhalla,
Sukhwinder K. Bhullar,
Adriana Adameova,
Karina Oliveira Mota,
Carla Maria Lins de Vasconcelos. Status of β1-Adrenoceptor Signal Transduction System in Cardiac Hypertrophy and Heart Failure. Rev. Cardiovasc. Med.2023, 24(9), 264.
https://doi.org/10.31083/j.rcm2409264
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Fig. 1.
Acute and chronic effects of the sympathetic nervous system on
-adrenoceptor-mediated signal transduction components. NE,
norepinephrine; EPI, epinephrine; Gs-Proteins, stimulatory guanine nucleotide
proteins; , increased.
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