Detrimental effects of beta-adrenergic stimulation on beta-adrenoceptors and microtubules in the heart.
Increased plasma catecholamines - in particular, excessive beta-adrenoceptor activation in chronic heart failure - may easily desensitize the beta-adrenoceptors as well as the postreceptor signal transductions. Since these detrimental changes in the failing heart could be reversible, administration of low-dose beta-blocker, which minimizes the negative inotropic effects, may be effective in attenuating the harmful effects of sympathetic nerve activation. Beta-adrenoceptor stimulation may also produce microtubule disruptions of the cell either through direct action or through an increase in heart rate. Treatment with beta-blockers could attenuate Ca overload by slowing the heart rate and may be useful as a protection from the structural disintegration of the cell. Thus, to clarify the underlying mechanisms of beta-blocker therapy for chronic heart failure, we have to consider not only to the functional aspects but also to the structural changes of the cells.
Hori
M
M
First Department of Medicine, Osaka University School of Medicine, Japan.
Koretsune
Y
Y
Sato
H
H
Kagiya
T
T
Kitabatake
A
A
Kamada
T
T
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009206:Myocardium / Q000473:pathology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta