Yao Hui, Tu Jie, Shan Qi-xian, Xia Qiang
School of Basic Medicine, Hangzhou Normal University Hangzhou 310036, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009 May;25(2):228-32.
To investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.
Experimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.
(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.
ET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.
研究内皮素 -1（ET -1）和一氧化氮（NO）对脂多糖（LPS）诱导的心肌功能障碍的影响，并探讨相关潜在机制。
通过腹腔注射LPS（10 mg·kg⁻¹）建立实验性脓毒症模型。在离体大鼠心脏上进行研究，以确定ET -1和NO在LPS对心脏收缩性影响中的作用；在离体大鼠心室肌细胞模型上观察心肌细胞内[Ca²⁺]i稳态。
（1）LPS处理4小时后，血清NO₂⁻/NO₃⁻水平和血浆ET -1水平显著升高。（2）LPS导致离体灌注大鼠心脏的心率 - 压力乘积（RPP）降低，左心室舒张末期压力（LVEDP）升高。用氨基胍（AMG）（100 mg·kg⁻¹，腹腔注射）或BQ -123（1 mg·kg⁻¹，腹腔注射）预处理可部分减轻LPS诱导的心肌抑制。当同时给予这两种药物时，LPS引起的心肌抑制几乎被消除。（3）与对照细胞相比，LPS显著降低咖啡因诱导的[Ca²⁺]i瞬变幅度。LPS处理大鼠的心肌细胞中肌浆网Ca²⁺ -ATP酶活性显著降低。单独用AMG或BQ -123预处理并不能减轻LPS诱导的肌浆网Ca²⁺ -ATP酶损伤。
ET -1和NO介导离体心脏的心肌功能障碍，并降低LPS处理大鼠心肌细胞内的[Ca²⁺]i瞬变。但ET -1和NO均不参与LPS诱导的肌浆网Ca²⁺ -ATP酶损伤。
