Deficiency of type 1 cannabinoid receptors worsens acute heart failure induced by pressure overload in mice

Yulin Liao, Jianping Bin, Masanori Asakura, Wanling Xuan, Baihe Chen, Qiaobing Huang, Dingli Xu, Catherine Ledent, Seiji Takashima, Masafumi Kitakaze

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

AimsWe 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.Methods and resultsAcute 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. ConclusionEndogenous activation of CB1 in mice has cardiac protection in AHF, which is attributable to the inhibition of excessive sympathetic activation.

Original languageEnglish (US)
Pages (from-to)3124-3133
Number of pages10
JournalEuropean Heart Journal
Volume33
Issue number24
DOIs
StatePublished - Dec 1 2012
Externally publishedYes

Keywords

  • Acute heart failure
  • Cannabinoid receptor
  • Catecholamine
  • Mortality
  • Mouse

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Liao, Y., Bin, J., Asakura, M., Xuan, W., Chen, B., Huang, Q., Xu, D., Ledent, C., Takashima, S., & Kitakaze, M. (2012). Deficiency of type 1 cannabinoid receptors worsens acute heart failure induced by pressure overload in mice. European Heart Journal, 33(24), 3124-3133. https://doi.org/10.1093/eurheartj/ehr246