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.
First Department of Medicine, Osaka University School of Medicine, Japan.
M
M
Hori
Y
Y
Koretsune
H
H
Sato
T
T
Kagiya
A
A
Kitabatake
T
T
Kamada
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