Recent studies have identified a missense mutation in the β1-receptor (ADRB1-A187V) that exerts a pronounced impact on human sleep, with a noted decrease in protein abundance in vivo. The administration of β-blockers is frequently associated with sleep disturbances in clinical settings. In this study, we assessed the influence of various β-blockers on sleep within mouse models. Our findings indicated that β-blockers could induce varying degrees of arousal, sleep disruption, and a decrease in REMS (rapid eye movement sleep). We examined the dose-dependent effects of metoprolol and nebivolol on both sleep and cardiac functionality in both wild-type and Adrb1-A187V mutant mice. Our data suggested that, in contrast to cardiac effects, higher doses of metoprolol are required to have noted impact on sleep. No genotype effect was observed with metoprolol in terms of sleep or cardiac function. In contrast, the mutant mice demonstrated increased sensitivity to nebivolol, which exacerbated sleep fragmentation and impeded the onset of REMS. This study is expected to provide some reference for minimizing the occurrence of sleep disorders and reducing the adverse reactions of drugs to the greatest extent.

Objective To observe the effects of restricted and high-fat diets on behavioral changes of wild-type(Adrb1+/+)and transgenic mice carrying Adrb1-A187V mutation(Adrb1+/m)with short sleep durations.Methods Adrb1+/+and Adrb1+/m C57BL/6 mice were randomized into normal chow group(25 Adrb1+/+and 26 Adrb1+/m mice for behavioral monitoring),odor retention fasting group(17 Adrb1+/+and 19 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+mice and 6 Adrb1+/m mice for EEG/EMG monitoring),absolute fasting group(6 Adrb1+/+and 4-5 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring),and high-fat diet group(6 Adrb1+/+and 7 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring).Electrodes for EEG and muscle activity monitoring were implanted on the skulls of the mice.After 24 h of odor retention fasting,absolute fasting,or high-fat feeding,the mice were observed for behavioral changes adapted to diet changes.Results In odor retention fasting experiment,Adrb1+/m mice exhibited more stable fluctuations of activities with mildly reduced movement and prolonged sleep duration,indicating enhanced starvation resistance.In absolute fasting experiment,Adrb1+/m mice showed significantly increased nighttime water intake,improved rhythmicity in water intake(frequent intakes in small amounts),and increased duration of non-rapid eye movement sleep(NREM).In the high-fat diet experiment,Adrb1+/m mice showed higher levels of activity with increased instances of nighttime rearing,longer movement distances,and increased rapid eye movement sleep during daytime.Conclusion Adrb1+/m mice can quickly respond to environmental changes and under restricted dietary conditions,they can conserve energy by increasing sleep to maintain energy homeostasis but show higher levels of activity under high-fat dietary conditions.

Objective To observe the effects of restricted and high-fat diets on behavioral changes of wild-type(Adrb1+/+)and transgenic mice carrying Adrb1-A187V mutation(Adrb1+/m)with short sleep durations.Methods Adrb1+/+and Adrb1+/m C57BL/6 mice were randomized into normal chow group(25 Adrb1+/+and 26 Adrb1+/m mice for behavioral monitoring),odor retention fasting group(17 Adrb1+/+and 19 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+mice and 6 Adrb1+/m mice for EEG/EMG monitoring),absolute fasting group(6 Adrb1+/+and 4-5 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring),and high-fat diet group(6 Adrb1+/+and 7 Adrb1+/m mice for behavioral monitoring;6 Adrb1+/+and 6 Adrb1+/m mice for EEG/EMG monitoring).Electrodes for EEG and muscle activity monitoring were implanted on the skulls of the mice.After 24 h of odor retention fasting,absolute fasting,or high-fat feeding,the mice were observed for behavioral changes adapted to diet changes.Results In odor retention fasting experiment,Adrb1+/m mice exhibited more stable fluctuations of activities with mildly reduced movement and prolonged sleep duration,indicating enhanced starvation resistance.In absolute fasting experiment,Adrb1+/m mice showed significantly increased nighttime water intake,improved rhythmicity in water intake(frequent intakes in small amounts),and increased duration of non-rapid eye movement sleep(NREM).In the high-fat diet experiment,Adrb1+/m mice showed higher levels of activity with increased instances of nighttime rearing,longer movement distances,and increased rapid eye movement sleep during daytime.Conclusion Adrb1+/m mice can quickly respond to environmental changes and under restricted dietary conditions,they can conserve energy by increasing sleep to maintain energy homeostasis but show higher levels of activity under high-fat dietary conditions.

Aim To investigate the relationship between monocyte chemoattractant protein-1(MCP-1) and pulmonary artery hypertension after acute pulmonary thromboembolism(PTE), and to explore the effects and mechanisms of resveratrol with MCP-1 in the acute PTE as well.Methods The acute PTE model of Sprague-Dawley rats was replicated using self-thrombosis.The rats were randomly divided into five groups(Normal, Solvent, acute PTE, antibody Cl142, and resveratrol), and 1h, 4h, 8h and 3 points were observed in each group.A model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter.Resveratrol or Cl142, dissolved in 1％ dimethyl sulfoxide(DMSO), was administered to the animals through caudalvein 1 h prior to the beginning of acute PTE modeling.Rats in normal control group and solvent control group were injected with normal saline and 1％ DMSO respectively.The mean pulmonary artery pressure(MPAP) and the mRNA and protein expression of MCP-1 were measured at each time point.Results ① The acute PTE group MPAP, MCP-1 mRNA and protein expression were significantly higher than those of the control group(P<0.05) at the same time;② The resveratrol group′s MPAP and MCP-1 mRNA, protein expression were significantly lower than those of the acute PTE group(P<0.05) at the same time;③ The Cl142 group MPAP and MCP-1 mRNA, protein expression were markedly reduced in the acute PTE group(P<0.05) at the same time.Conclusions The large expression of MCP-1 after acute PTE is involved in the formation of pulmonary hypertension after acute PTE.Resveratrol can reduce the pressure of pulmonary artery after acute PTE by down-regulating the MCP-1 expression.