Cardiac dysfunction in aging conscious rats: altered cardiac cytoskeletal proteins as a potential mechanism.
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 (tau) 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 beta-adrenergic receptor stimulation with dobutamine (20 mug/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%), alpha-tubulin (92%), and beta-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.
Lieber
Samuel C
SC
Dept. of Cell Biology & Molecular Medicine, UMDNJ-New Jersey Medical School, 185 South Orange Ave., MSB G-609, Newark, NJ 07103, USA.
Qiu
Hongyu
H
Chen
Li
L
Shen
You-Tang
YT
Hong
Chull
C
Hunter
William C
WC
Aubry
Nadine
N
Vatner
Stephen F
SF
Vatner
Dorothy E
DE
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D003187:Compliance; D003243:Consciousness; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003893:Desmin / Q000378:metabolism; D004280:Dobutamine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure
D000318:Adrenergic beta-Agonists; D003598:Cytoskeletal Proteins; D003893:Desmin; D014404:Tubulin; D004280:Dobutamine; D003094:Collagen