Department of Cardiology, and Organ Failure Key Laboratory of Ministry of Education, Nanfang Hospital, Southern Medical University, 1838 Guangzhou avenue north, Guangzhou 510515, China.
Eur Heart J. 2012 Dec;33(24):3124-33. doi: 10.1093/eurheartj/ehr246. Epub 2011 Jul 23.
We investigated the influence of type one cannabinoid receptor (CB1) deficiency on acute heart failure (AHF) and the underlying mechanism. Acute heart failure syndrome is an important clinical problem because of its high morbidity and mortality rates. Activation of CB1 induces vascular dilation and reinforces the properties of morphine, long-standing therapies for AHF syndrome, but the effect of endogenous CB1 activation on AHF is largely unknown.
Acute heart failure mouse model characterized by hypertension and pulmonary oedema was created by using transverse aortic constriction (TAC). Mortality, echocardiography, haemodynamic, morphology, and circulatory catecholamine levels in response to TAC were evaluated in CB1 knockout (KO) and wild-type mice. Type one cannabinoid receptor KO mice had a much higher mortality rate at 1 week after TAC attributable to AHF (65 vs. 11%, P< 0.001). One hour after TAC, CB1 KO mice had significant larger lung weight to body weight ratio (LW/BW, 14.53 + 1.09 mg/g in KO vs. 10.42 + 0.36 mg/g in WT, P < 0.01) and higher plasma epinephrine levels (9720 + 1226 pg/mL vs. 6378 + 832 pg/mL, P < 0.05). Pharmacological activation of CB1 reduced LW/BW in wild-type mice. Administration of epinephrine to wild-type TAC mice significantly increased left ventricular end-diastolic pressure and LW/BW, while CB1 agonists reduced the LW/BW and the plasma levels of catecholamine and increased myocardial activity of AMP-activated protein kinase.
Endogenous activation of CB1 in mice has cardiac protection in AHF, which is attributable to the inhibition of excessive sympathetic activation.
我们研究了 1 型大麻素受体 (CB1) 缺失对急性心力衰竭 (AHF) 的影响及其潜在机制。急性心力衰竭综合征是一个重要的临床问题，因为其发病率和死亡率都很高。CB1 的激活会引起血管扩张，并增强吗啡的作用，吗啡是治疗 AHF 综合征的长期疗法，但内源性 CB1 激活对 AHF 的影响在很大程度上尚不清楚。
通过横主动脉缩窄 (TAC) 建立了高血压和肺水肿为特征的急性心力衰竭小鼠模型。在 CB1 敲除 (KO) 和野生型小鼠中评估了 TAC 后死亡率、超声心动图、血流动力学、形态和循环儿茶酚胺水平。TAC 后 1 周，CB1 KO 小鼠的死亡率明显更高，归因于 AHF (65% vs. 11%，P<0.001)。TAC 后 1 小时，CB1 KO 小鼠的肺重与体重比 (LW/BW) 显著增大 (14.53 + 1.09 mg/g 在 KO 中比 10.42 + 0.36 mg/g 在 WT 中，P<0.01)，血浆肾上腺素水平升高 (9720 + 1226 pg/mL 在 KO 中比 6378 + 832 pg/mL 在 WT 中，P<0.05)。CB1 的药理学激活降低了野生型小鼠的 LW/BW。肾上腺素给药显著增加了野生型 TAC 小鼠的左心室舒张末期压和 LW/BW，而 CB1 激动剂降低了 LW/BW 和儿茶酚胺的血浆水平，并增加了心肌 AMP 激活蛋白激酶的活性。
在 AHF 中，小鼠内源性 CB1 的激活具有心脏保护作用，这归因于对过度交感神经激活的抑制。
