Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats
Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats
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DOI：
10.1161/01.hyp.0000184230.52059.33
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发表时间：
2005-10-01
期刊：
影响因子：
8.3
通讯作者：
Shroff, SG
中科院分区：
文献类型：
--
作者：
Debrah, DO;Conrad, KP;Shroff, SG
对清醒的血压正常大鼠（雄性和雌性）长期给予重组人松弛素（rhRLX）可增加心输出量（CO）和总动脉顺应性（AC（g）），并降低全身血管阻力（SVR），而平均动脉压（MAP）无变化。松弛素对高血压动物模型全身血流动力学和动脉特性的影响（幅度和时间模式）尚不清楚。因此，本研究的主要目的是确定rhRLX在高血压大鼠中的心血管作用，使用2种模型：长期给予血管紧张素II（AII）的Long-Evans大鼠和自发性高血压大鼠（SHR）。CO和全身动脉负荷，定量SVR和ACg，获得使用我们以前报道的方法。在AN诱导的高血压大鼠中，急性rhRLX给药（长达6小时）显著增加了CO和AC（g）（分别比基线高24.9 +/- 3.9和34.3 +/- 12.6%），显著降低了SVR（17.2 +/- 3.5%），而没有改变MAP。与此相反，急性rhRLX给药SHR和正常血压大鼠长达6小时未能产生任何显着的变化，CO，ACg，SVR，或MAP。然而，对SHR的长期rhRLX给药（1 - 7天）产生了显著变化（CO和AC（g）分别增加24.0 +/- 8.1和22.3 +/- 6.6%，SVR降低13.3 +/- 5.3%，MAP无变化）。总之，rhRLX增加高血压大鼠的CO和降低动脉负荷，而不降低MAP。然而，对rhRLX治疗的反应的时间过程依赖于高血压模型，使得以All介导的高血压为特征的大鼠比SHR对rhRLX给药反应更快。
Chronic administration of recombinant human relaxin (rhRLX) to conscious, normotensive rats (male and female) increases cardiac output (CO) and global arterial compliance (AC(g)) and reduces systemic vascular resistance (SVR) with no change in mean arterial pressure (MAP). Effects (magnitude and temporal pattern) of relaxin on systemic hemodynamics and arterial properties in hypertensive animal models are not known. Accordingly, the major goal of the present study was to determine the cardiovascular effects of rhRLX in hypertensive rats using 2 models: Long-Evans rats chronically administered angiotensin II (AII) and spontaneously hypertensive rats (SHR). CO and systemic arterial load, as quantified by SVR and ACg, were obtained using methods reported previously by us. In rats with An-induced hypertension, acute rhRLX administration (up to 6 hours) significantly increased CO and AC(g) (24.9 +/- 3.9 and 34.3 +/- 12.6% above baseline, respectively) and significantly decreased SVR (17.2 +/- 3.5%) without changing, MAP. In contrast, acute rhRLX administration to SHR and normotensive rats for up to 6 hours failed to produce any significant changes in CO, ACg, SVR, or MAP. However, chronic rhRLX administration (I to 7 days) to SHR yielded significant changes (24.0 +/- 8.1 and 22.3 +/- 6.6% increases in CO and AC(g), respectively, and a 13.3 +/- 5.3% decrease in SVR, with no change in MAP). In conclusion, rhRLX increases CO and reduces arterial load in hypertensive rats without reducing MAP. However, the time course of response to rhRLX treatment is dependent on the model of hypertension such that rats characterized by All-mediated hypertension responded more rapidly to rhRLX administration than SHR.