Lookin Oleg, Balakin Alexander, Kuznetsov Daniil, Protsenko Yuri
Laboratory of Biological Motility, Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation.
Clin Exp Pharmacol Physiol. 2015 Nov;42(11):1198-206. doi: 10.1111/1440-1681.12471.
The length-dependent activation of contraction is attenuated in the failing myocardium of adult male rats. This pathological change is not seen in adult female rats, possibly because of a protective effect of sex hormones. The present study evaluated length-dependent changes in isometric twitch, Ca(2+) transient (CaT) and action potential (AP) in the right ventricular myocardium of impuberal healthy male and female rats (control) and in rats treated with a single injection of 50 mg/kg monocrotaline (MCT). Compared with sex-matched control rats, MCT-treated male and female rats exhibited increased right ventricular weight (134% and 142% of control, respectively), decreased left ventricular weight (72% and 79%), twitch attenuation (48.8 ± 2.7% and 57.5 ± 1.2%) and prolongation (125 ± 3% and 127 ± 2%), CaT attenuation (37.8 ± 0.4% and 39.1 ± 1.1%) and prolongation (114 ± 1% and 116 ± 1%) and AP prolongation at 90% repolarization (195 ± 2% and 203 ± 1%). The MCT-treated male rats exhibited a 50% lower integral magnitude and an approximately 25% larger time-to-peak 'bump' compared with control male rats. These parameters in MCT-treated female rats tended to show similar changes to those seen in the control female rats, with no significant difference between the two groups. In all groups, integral magnitude and time-to-peak 'bump' increased with length. In conclusion, the length-dependent activation of contraction was equally blunted in the failing right ventricular myocardium of impuberal male and female rats. This was related to changes in CaT and AP, which were similar between male and female rats. Therefore, puberty is necessary for manifestation of the protective effects of sex hormones on this remodelling.
成年雄性大鼠衰竭心肌中长度依赖性收缩激活减弱。成年雌性大鼠未见这种病理变化,可能是由于性激素的保护作用。本研究评估了未成熟健康雄性和雌性大鼠(对照组)以及单次注射50mg/kg野百合碱(MCT)处理的大鼠右心室心肌等长收缩、Ca(2+)瞬变(CaT)和动作电位(AP)的长度依赖性变化。与性别匹配的对照大鼠相比,MCT处理的雄性和雌性大鼠右心室重量增加(分别为对照组的134%和142%),左心室重量降低(72%和79%),收缩减弱(48.8±2.7%和57.5±1.2%)和延长(125±3%和127±2%),CaT减弱(37.8±0.4%和39.1±1.1%)和延长(114±1%和116±1%)以及90%复极化时AP延长(195±2%和203±1%)。与对照雄性大鼠相比,MCT处理的雄性大鼠积分幅度降低50%,峰时“凸起”时间大约长25%。MCT处理的雌性大鼠的这些参数变化趋势与对照雌性大鼠相似,两组之间无显著差异。在所有组中,积分幅度和峰时“凸起”时间随长度增加。总之,未成熟雄性和雌性大鼠衰竭右心室心肌中长度依赖性收缩激活同样减弱。这与CaT和AP的变化有关,雄性和雌性大鼠的这些变化相似。因此,青春期对于性激素对这种重塑的保护作用的表现是必要的。