Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal aging of the rodent heart results in prominent prolongation of the twitch. We tested the hypothesis that increased expression of beta-myosin heavy chain (MHC), as occurs in the normal aging process in the rodent heart, contributes to the prolongation of the twitch by depressing the kinetics of cross-bridge interaction. Using 3-, 9-, 21-, and 33-mo-old male Fischer 344 x Brown Norway F1 hybrid rats, we examined both the rate of tension development (kCa) and unloaded shortening velocity in chemically skinned myocardium. Although kCa in all four age groups was dependent on the level of Ca2+ activation, both submaximal and maximal kCa were significantly slower in 9-, 21-, and 33-mo-old rats relative to 3-mo-old rats. Furthermore, unloaded shortening velocity was significantly reduced in 9-, 21-, and 33-mo-old rats compared with 3-mo-old rats. Collectively, these data strongly suggest that the aging-related increase in beta-MHC expression results in a progressive slowing of cross-bridge interaction kinetics in skinned myocardium, which most likely contributes to the overall aging-dependent reduction in myocardial functional capacity.
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PMID:Aging-dependent depression in the kinetics of force development in rat skinned myocardium. 1033 Feb 33

The Fischer 344 x Brown Norway (F344xBN) rat has been demonstrated to have a lower incidence of age-related pathology than other rat strains. Therefore, to elucidate the effects of aging on cardiac function, uncomplicated by compensatory effects caused by age-related pathology, cardiac myocytes were isolated from female F344xBN rats at 6 (young) and 32-33 (old) mo of age. Myocytes showed an increase in the relative amount of beta-myosin heavy chain with advanced age and a significant rightward shift in the tension-pCa curve from 5.78 +/- 0.02 pCa units in young adult myocytes to 5.66 +/- 0.03 pCa units. Consistent with a shift to a slower myosin isoform, the time from stimulation to peak sarcomere shortening increased with age from 50.5 +/- 1.3 to 58.9 +/- 1.0 ms. In contrast, no age-related difference was found in either the relengthening parameters or the Ca(2+) transient, indicating that relaxation is not directly altered by aging. This latter finding is at variance with previous studies in rat strains with higher rates of pathology. We conclude, therefore, that the primary effect of aging in isolated cardiac myocytes from the F344xBN rat model is a shift in the myosin heavy chain isoform. Changes in relaxation seen in other rat strains may result from compensatory mechanisms induced by pathological conditions.
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PMID:Effects of aging on single cardiac myocyte function in Fischer 344 x Brown Norway rats. 1092 54