TY - JOUR
T1 - Deficiency of type 1 cannabinoid receptors worsens acute heart failure induced by pressure overload in mice
AU - Liao, Yulin
AU - Bin, Jianping
AU - Asakura, Masanori
AU - Xuan, Wanling
AU - Chen, Baihe
AU - Huang, Qiaobing
AU - Xu, Dingli
AU - Ledent, Catherine
AU - Takashima, Seiji
AU - Kitakaze, Masafumi
N1 - Funding Information:
This work was supported by grants from the Department of Education of Guangdong Provincial Government and the Southern Medical University, China (to Y.L.), the Japanese Ministry of Education, Culture, Sports, Science and Technology, Japan Heart Foundation, and Japan Cardiovascular Research Foundation (to M.K.).
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - Acute heart failure
KW - Cannabinoid receptor
KW - Catecholamine
KW - Mortality
KW - Mouse
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U2 - 10.1093/eurheartj/ehr246
DO - 10.1093/eurheartj/ehr246
M3 - Article
C2 - 21785110
AN - SCOPUS:84871180851
SN - 0195-668X
VL - 33
SP - 3124
EP - 3133
JO - European Heart Journal
JF - European Heart Journal
IS - 24
ER -