Contractile response of individual cardiac myocytes to norepinephrine declines with senescence.
The present study utilized individual isolated left ventricular cardiac myocytes from hearts of animals of a broad age range to evaluate the response to norepinephrine and to other stimuli that augment myocardial cell contractile performance. During electrical stimulation before drugs neither the amplitude nor the velocity of shortening normalized for resting cell length differed among cells isolated from 2-, 6- to 8-, or 24-mo-old animals. Norepinephrine augmented twitch amplitude and velocity about fourfold in cells from 2-mo-old hearts but only by 2.5-fold in cells from 24-mo-old hearts (age effect, P less than 0.001). In contrast, the contractile response to increases in bathing [Ca2+] or to the addition of the calcium channel agonist BAY K 8644 or of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT cAMP) did not vary with age. These results indicate that the age-associated contractile deficit during beta-adrenergic stimulation is specific to the beta-adrenergic pathway and an age-associated deficit in the net production of cAMP. This can be attributed to a diminished cardiac myocyte response to beta-adrenergic agonists, in contrast to modulation of the beta-adrenergic response by other receptor agonists, which are present in intact tissue but absent under the conditions of the present study.
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
M
M
Sakai
R S
RS
Danziger
R P
RP
Xiao
H A
HA
Spurgeon
E G
EG
Lakatta
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002469:Cell Separation; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D006352:Heart Ventricles; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D009638:Norepinephrine / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine