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首页> 外文期刊>Life sciences >Functional and molecular effects of imidazoline receptor activation in heart failure.
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Functional and molecular effects of imidazoline receptor activation in heart failure.

机译：咪唑啉受体激活在心力衰竭中的功能和分子作用。

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AIMS: Heart failure is a progressive deterioration in heart function associated with overactivity of the sympathetic nervous system. The benefit of inhibition of sympathetic activity by moxonidine, a centrally acting imidazoline receptor agonist, was questioned based on the outcome of a failing clinical trial. The following studies measured cardiac structure and hemodynamics and mechanisms underlying moxonidine-induced changes, in cardiomyopathic hamsters, where the stage of the disease, dose, and compliance were controlled. MAIN METHODS: Male BIO 14.6 hamsters (6 and 10 months old, with moderate and advanced heart failure, respectively) received moxonidine at 2 concentrations: low (2.4 mg/kg/day) and high (9.6 mg/kg/day), or vehicle, subcutaneously, for 1month. Cardiac function was measured by echocardiography, plasma and hearts were collected for histological determination of fibrosis and apoptosis, as well as for measurement cytokines by Elisa and cardiac proteins by Western blotting. KEY FINDINGS: Compared to age-matched vehicle-treated BIO 14.6, moxonidine did not reduce blood pressure but significantly reduced heart rate and improved cardiac performance. Moxonidine exerted anti-apoptotic effect with differential inflammatory/anti-inflammatory responses that culminate in attenuated cardiac apoptosis and fibrosis and altered protein expression of collagen types. Some effects were observed regardless of treatment onset, although the changes were more significant in the younger group. Interestingly, moxonidine resulted in upregulation of cardiac imidazoline receptors. SIGNIFICANCE: These studies imply that in addition to centrally mediated sympathetic inhibition, the effects of moxonidine may, at least in part, be mediated by direct actions on the heart. Further investigation of imidazolines/imidazoline receptors in cardiovascular diseases is warranted.
机译：目的：心力衰竭是与交感神经系统过度活动有关的心脏功能的逐步恶化。基于一项失败的临床试验的结果，人们质疑了莫索尼定（一种中枢作用的咪唑啉受体激动剂）抑制交感神经活动的益处。以下研究测量了心肌病仓鼠中心脏的结构，血流动力学以及由莫索尼定引起的变化的机制，该病的阶段，剂量和依从性得到控制。主要方法：雄性BIO 14.6仓鼠（分别为6和10个月大，分别患有中度和晚期心力衰竭）接受莫索尼定2种浓度：低（2.4 mg / kg /天）和高（9.6 mg / kg /天），或皮下注射1个月。通过超声心动图测量心脏功能，收集血浆和心脏用于组织学测定纤维化和细胞凋亡，以及通过Elisa测量细胞因子和通过蛋白质印迹法测量心脏蛋白。主要发现：与年龄匹配的媒介物治疗的BIO 14.6相比，莫索尼定不会降低血压，但可以显着降低心率并改善心脏性能。莫索尼定具有抗凋亡作用，并具有不同的炎症/抗炎反应，最终导致减弱的心脏凋亡和纤维化以及改变胶原蛋白的蛋白质表达。不管治疗的开始如何，都观察到一些效果，尽管在年轻组中变化更为明显。有趣的是，莫索尼定导致心脏咪唑啉受体的上调。意义：这些研究表明，除中枢介导的交感神经抑制作用外，莫索尼定的作用可能至少部分地由对心脏的直接作用介导。需进一步研究咪唑啉/咪唑啉受体在心血管疾病中的作用。

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