Exogenously administered growth hormone and insulin-like growth factor-I alter intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation in the isolated isovolumic buffer-perfused rat heart.
Exogenously administered growth hormone and insulin-like growth factor-I alter intracellular Ca2+ handling and enhance cardiac performance. In vitro evaluation in the isolated isovolumic buffer-perfused rat heart.
复制标题
外源性施用生长激素和胰岛素样生长因子-I 可以改变细胞内 Ca2+ 的处理并增强心脏功能。
DOI：
10.1161/01.res.79.2.227
复制
发表时间：
1996
影响因子：
20.1
通讯作者：
Morgan,JP
中科院分区：
文献类型：
--
作者：
Strömer,H;Cittadini,A;Douglas,PS;Morgan,JP
已经提出，在大鼠中用生长激素（GH）或胰岛素样生长因子-I（IGF-I）的慢性治疗可以增强体内心脏功能。为了证实这些发现，并阐明心脏功能调制的机制，我们研究了高剂量的GH和IGF-I单独或联合治疗4周后，离体缓冲液灌注大鼠心脏。在发生最大发展压力（DevP）的心内球囊体积的50%处测量机械参数。通过逐步增加灌流液中的Ca 2+，并绘制收缩期壁应力（σs）与细胞内峰值收缩期Ca 2+（用水母发光蛋白生物发光法测量）的关系，评估力-Ca 2+关系的EC 50和最大Ca 2+激活的收缩期壁应力（max σs）。与对照组相比，治疗组收缩压（Ps）、DevP和（+dP/dt）/DevP均显著升高。联合用药组的作用减弱。当灌流液Ca ~（2+）浓度> 1.5mmol/L时，各处理组的σ s均增加。增强的收缩性能可以解释为由于对Ca 2+的最大反应增加而导致的总体Ca 2+反应性增加，即使Ca 2+剂量反应的EC 50也略有增加。PS进一步增强的相对壁厚的增加所诱导的治疗。舒张压、舒张期Ca 2+以及Ca 2+瞬变的幅度和时程不受任何治疗方案的影响。所有治疗均导致体重和心脏重量增加。这些数据支持IGF-I和GH通过改变心脏几何形状以及通过提高最大σs直接影响心脏性能的假设。
It has been proposed that chronic treatment with growth hormone (GH) or insulin-like growth factor-I (IGF-I) in the rat may enhance cardiac function in vivo. To confirm these findings and elucidate the mechanisms by which cardiac function is modulated, we studied isolated buffer-perfused rat hearts after 4 weeks of treatment with high doses of GH and IGF-I alone or in combination. Mechanical parameters were measured at 50% of the intracardiac balloon volume at which maximal developed pressure (DevP) occurred. EC50of the force-Ca2+relationship and maximal Ca2+-activated systolic wall stress (max σs) were assessed by increasing Ca2+in the perfusate in a stepwise fashion and plotting systolic wall stress (σs) versus intracellular peak systolic Ca2+, measured by the aequorin bioluminescence method. We found a marked increase of systolic pressure (Ps), DevP, and (+dP/dt)/DevP in the treated groups compared with the control group. The combination group showed a blunted effect. σswas increased in all treated groups for a perfusate Ca2+concentration of >1.5 mmol/L. The enhanced systolic performance can be explained by an increase of the overall Ca2+responsiveness due to an increased maximal response to Ca2+even though the EC50of the Ca2+-dose response was also slightly increased. Pswas further enhanced by an increase of the relative wall thickness induced by the treatment. Diastolic pressure, diastolic Ca2+, and the amplitude and time course of the Ca2+transient were not influenced by any treatment protocol. All treatments caused increases of body and heart weight. These data support the hypothesis that both IGF-I and GH directly affect cardiac performance by altering cardiac geometry as well as by enhancing max σs.