Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil; Faculty of Medicine of the University of Strasbourg, Strasbourg, France.
Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Auton Neurosci. 2019 Mar;217:18-25. doi: 10.1016/j.autneu.2018.12.007. Epub 2018 Dec 22.
The objective of this study was to investigate the effects of a new I-imidazoline receptor-selective pyrroline compound on the hemodynamic, metabolic and microvascular alterations in a high-fat diet (HFD)-induced model of metabolic syndrome in rats.
In total, twenty adult male Wistar rats were fed a high-fat diet (HFD, n = 20) for 20 weeks. Thereafter, the rats received a new pyrroline compound selective for I1-imidazoline receptors (LNP599; 10 mg/kg/day) or vehicle (n = 10/group) orally by gavage for 4 weeks. Functional microcirculation was assessed using intravital video microscopy, and structural microcirculation was evaluated using histochemical analysis.
LNP599 induced concomitant reductions in the SBP, HR and plasma catecholamine levels. The animals treated with this new antihypertensive compound also presented an improvement in body weight and the metabolic parameters related to metabolic syndrome, such as the glucose and lipid profiles. These effects were accompanied by a reversal of the functional and structural capillary rarefaction in the skeletal muscle.
The modulation of the sympathetic nervous system by a selective agonist for I-imidazoline receptors improves the hemodynamic and metabolic parameters in an experimental model of metabolic syndrome. LNP599 can also contribute to the restoration of microcirculatory parameters.
本研究旨在探讨新型 I-咪唑啉受体选择性吡咯烷化合物对高脂饮食（HFD）诱导的代谢综合征大鼠模型血流动力学、代谢和微血管改变的影响。
共 20 只成年雄性 Wistar 大鼠接受高脂饮食（HFD，n=20）喂养 20 周。此后，大鼠通过灌胃接受新型 I1-咪唑啉受体选择性吡咯烷化合物（LNP599；10mg/kg/天）或载体（每组 n=10）治疗 4 周。使用活体视频显微镜评估功能性微循环，使用组织化学分析评估结构微循环。
LNP599 诱导 SBP、HR 和血浆儿茶酚胺水平同时降低。用这种新型抗高血压化合物治疗的动物还改善了体重和与代谢综合征相关的代谢参数，如血糖和血脂谱。这些作用伴随着骨骼肌中功能性和结构性毛细血管稀疏的逆转。
通过选择性激动剂调节交感神经系统可改善代谢综合征实验模型的血流动力学和代谢参数。LNP599 还可以有助于恢复微循环参数。
