衰老大鼠心脏血管紧张素Ⅱ受体对α_1肾上腺素受体正性变力效应的影响

目的研究激动血管紧张素Ⅱ(AngⅡ)1型受体(AT1R)和2型受体(AT2R)对α1肾上腺素受体(α1-AR)介导的心肌正性变力效应的影响,以及这种影响在大鼠心脏衰老过程中的变化。方法对于3.5、12、18、24月龄的Wistar大鼠采用体外左心房收缩功能实验,观察AngⅡ分别激动AT1R和AT2R对苯肾上腺素激动α1-AR介导正性变力效应的影响。结果在AT2R阻滞剂PD123319存在时,AngⅡ激动AT1R,与AngⅡ共同激动AT1R和AT2R时比较,3.5、12月龄大鼠α1-AR介导的正性变力效应的最大收缩效应(Rmax)及Rmax50%时的药物浓度值(以其负对数pD2值表示)差异均无显著性意义;18、24月龄大鼠Rmax及pD2值均增大。在AT1R阻滞剂氯沙坦存在时,AngⅡ激动AT2R,与AngⅡ共同激动AT1R和AT2R时比较,各月龄大鼠α1-AR介导的正性变力效应Rmax及pD2值差异均无显著性意义。结论随着鼠龄的增长,激动AT1R可增强大鼠心肌α1-AR介导的正性变力效应,而激动AT2R对α1-AR介导的心肌正性变力效应没有影响。

Effect of AT1 and AT2 receptors on α1-adrenoceptor-mediated inotropic response of heart in senescent rat

Objective To investigate the effect of angiotensin AT1 and AT2 receptors(AT1R,AT2R) on the alpha1-adrenoceptor(α1-AR)-mediated positive inotropic response of heart in rats of different ages.Method For rats at age of 3.5,12,18 and 24 months,inotropic response was determined by contractile function experiment in isolated electrically driven rat left atrium.Results No effect was found on the concentration-response-curve induced by phenylephrine(PE) when pretreatment of the preparations with AngⅡ and PD123319 in 3.5-or 12-month-old rats.However in 18-and 24-month-old rats,when pretreatment of the preparations with AngⅡ and PD123319, the maximum positive inotropic response induced by PE markedly increased and the pD2 significantly increased also.No effect was found on the concentration-response-curve induced by PE in the presence of AngⅡ and Losartan in rats of every age.Conclusions The activation of AT1R enhanced the positive inotropic response induced by the activation of α1-AR in isolated left atrium of senescent rats.The activation of AT2R had no effect on the positive inotropic response induced by the activation of α1-AR in rats of every age.