Dimethylthiourea normalizes velocity-dependent, but not force-dependent, index of ventricular performance in diabetic rats: role of myosin heavy chain isozyme

被引：4

作者：

Yeih, Dong-Feng ^{[1
]}

Yeh, Hung-I ^{[2
,3
,4
,5
]}

Hsin, Ho-Tsung ^{[1
]}

Lin, Lian-Yu ^{[6
]}

Chiang, Fu-Tien ^{[6
]}

Tseng, Chuen-Den ^{[6
]}

Chu, Shu-Hsun ^{[1
]}

Tseng, Yung-Zu ^{[6
]}

机构：

[1] Far Eastern Mem Hosp, Dept Cardiol, Pan Chiao, Taipei County, Taiwan

[2] Mackay Mem Hosp, Dept Internal Med, Taipei, Taiwan

[3] Mackay Mem Hosp, Dept Med Res, Taipei, Taiwan

[4] Mackay Med Coll, Taipei, Taiwan

[5] Taipei Med Univ, Taipei, Taiwan

[6] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 10016, Taiwan

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2009年 / 297卷 / 04期

关键词：

myocyte enhancer factor-2; transcription factor; contractile function; oxidative stress; antioxidant; ENHANCER FACTOR-2 MEF2; CARDIAC-HYPERTROPHY; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; TRANSCRIPTION FACTORS; IN-VIVO; ELECTROPHORETIC SEPARATION; CONTRACTILE DYSFUNCTION; SYSTOLIC RESISTANCE; LOADING CONDITIONS;

D O I：

10.1152/ajpheart.01269.2008

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Yeih DF, Yeh HI, Hsin HT, Lin LY, Chiang FT, Tseng CD, Chu SH, Tseng YZ. Dimethylthiourea normalizes velocity-dependent, but not force-dependent, index of ventricular performance in diabetic rats: role of myosin heavy chain isozyme. Am J Physiol Heart Circ Physiol 297: H1411-H1420, 2009. First published July 24, 2009; doi: 10.1152/ajpheart.01269.2008. Hydroxyl radicals and hydrogen peroxide are involved in the pathogenesis of systolic dysfunction in diabetic rats, but the precise mechanisms and the effect of antioxidant therapy in diabetic subjects have not been elucidated. We aimed to evaluate the effects of dimethylthiourea (DMTU), a potent hydroxyl radical scavenger, on both force-dependent and velocity-dependent indexes of cardiac contractility in streptozotocin (STZ)-induced early and chronic diabetic rats. Seventy-two hours and 8 wk after STZ (55 mg/kg) injection, diabetic rats were randomized to either DMTU (50 mg.kg(-1).day(-1) ip) or vehicle treatment for 6 and 12 wk, respectively. All rats were then subjected to invasive hemodynamic studies. Maximal systolic elastance (E-max) and maximum theoretical flow (Q(max)) were assessed by curve-fitting techniques in terms of the elastance-resistance model. Both normalized Emax (E-maxn) and afterload-adjusted Q(max) (Q(maxad)) were depressed in diabetic rats, concomitant with altered myosin heavy chain (MHC) isoform composition and its upstream regulators, such as myocyte enhancer factor-2 (MEF-2) and heart autonomic nervous system and neural crest derivatives ( HAND). In chronic diabetic rats, DMTU markedly attenuated the impairment in Q(maxad) and normalized the expression of MEF-2 and eHAND and MHC isoform composition but exerted an insignificant benefit on E-maxn. Regarding preventive treatment, DMTU significantly ameliorated both E-maxn and Q(maxad) in early diabetic rats. In conclusion, our study shows that DMTU has disparate effects on Q(maxad) and E-maxn in chronic diabetic rats. The advantage of DMTU in chronic diabetic rats might involve normalization of MEF-2 and eHAND, as well as reversal of MHC isoform switch.

引用

页码：H1411 / H1420

页数：10

共 2 条

[1] Inhibition of nitric oxide synthase normalizes force- and velocity-dependent indices of cardiac contractility in diabetic rats: roles of nitrosative stress and myosin heavy chain isoform switch
Yeih, Y. D. F.
Liao, L. P. C.
Tseng, T. Y. Z.
EUROPEAN HEART JOURNAL, 2010, 31 : 422 - 422
[2] DISPARATE EFFECTS OF EARLY PRESSURE-OVERLOAD HYPERTROPHY ON VELOCITY-DEPENDENT AND FORCE-DEPENDENT INDEXES OF VENTRICULAR PERFORMANCE IN THE CONSCIOUS BABOON
HOIT, BD
SHAO, YF
GABEL, M
WALSH, RA
CIRCULATION, 1995, 91 (04) : 1213 - 1220

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