TY - JOUR
T1 - Cardiac dysfunction in aging conscious rats
T2 - Altered cardiac cytoskeletal proteins as a potential mechanism
AU - Lieber, Samuel C.
AU - Qiu, Hongyu
AU - Chen, Li
AU - Shen, You Tang
AU - Hong, Chull
AU - Hunter, William C.
AU - Aubry, Nadine
AU - Vatner, Stephen F.
AU - Vatner, Dorothy E.
PY - 2008/8
Y1 - 2008/8
N2 - The objective of this study was to test the hypothesis that the mechanism mediating left ventricular (LV) dysfunction in the aging rat heart involves, in part, changes in cardiac cytoskeletal components. Our results show that there were no significant differences in heart rate, LV pressure, or LV diameter between conscious, instrumented young [5.9 ± 0.3 mo (n = 9)] and old rats [30.6 ± 0.1 mo (n = 10)]. However, the first derivative of LV pressure (LV dP/dt) was reduced (8,309 ± 790 vs. 11,106 ± 555 mmHg/s, P < 0.05) and isovolumic relaxation time (τ) was increased (8.7 ± 0.7 vs. 6.3 ± 0.6 ms, P < 0.05) in old vs. young rats, respectively. The differences in baseline LV function in young and old rats, which were modest, were accentuated after β-adrenergic receptor stimulation with dobutamine (20 μg/kg), which increased LV dP/dt by 170 ± 9% in young rats, significantly more (P < 0.05) than observed in old rats (115 ± 5%). Volume loading in anesthetized rats demonstrated significantly impaired LV compliance in old rats, as measured by the LV end-diastolic pressure and dimension relationship. In old rat hearts, there was a significant (P < 0.05) increase in the percentage of LV collagen (2.4 ± 0.2 vs. 1.3 ± 0.2%), α-tubulin (92%), and β-tubulin (2.3-fold), whereas intact desmin decreased by 51%. Thus the cardiomyopathy of aging in old, conscious rats may be due not only to increases in collagen but also to alterations in cytoskeletal proteins.
AB - The objective of this study was to test the hypothesis that the mechanism mediating left ventricular (LV) dysfunction in the aging rat heart involves, in part, changes in cardiac cytoskeletal components. Our results show that there were no significant differences in heart rate, LV pressure, or LV diameter between conscious, instrumented young [5.9 ± 0.3 mo (n = 9)] and old rats [30.6 ± 0.1 mo (n = 10)]. However, the first derivative of LV pressure (LV dP/dt) was reduced (8,309 ± 790 vs. 11,106 ± 555 mmHg/s, P < 0.05) and isovolumic relaxation time (τ) was increased (8.7 ± 0.7 vs. 6.3 ± 0.6 ms, P < 0.05) in old vs. young rats, respectively. The differences in baseline LV function in young and old rats, which were modest, were accentuated after β-adrenergic receptor stimulation with dobutamine (20 μg/kg), which increased LV dP/dt by 170 ± 9% in young rats, significantly more (P < 0.05) than observed in old rats (115 ± 5%). Volume loading in anesthetized rats demonstrated significantly impaired LV compliance in old rats, as measured by the LV end-diastolic pressure and dimension relationship. In old rat hearts, there was a significant (P < 0.05) increase in the percentage of LV collagen (2.4 ± 0.2 vs. 1.3 ± 0.2%), α-tubulin (92%), and β-tubulin (2.3-fold), whereas intact desmin decreased by 51%. Thus the cardiomyopathy of aging in old, conscious rats may be due not only to increases in collagen but also to alterations in cytoskeletal proteins.
KW - Aging cardiomyopathy
KW - Left ventricular diastolic function
KW - Left ventricular systolic function
KW - Tubulin
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U2 - 10.1152/ajpheart.00146.2008
DO - 10.1152/ajpheart.00146.2008
M3 - Article
C2 - 18567712
AN - SCOPUS:52449102483
SN - 0363-6135
VL - 295
SP - H860-H866
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2
ER -