血管紧张素Ⅱ对不同年龄大鼠异丙基肾上腺素激动β受体效应的影响

Effects of angiotensin Ⅱ on the action of β-adrenoceptor stimulated by isoprenalin in Sprague-Dawley rats

目的 研究 3 5月龄与 12 0月龄SD大鼠心脏血管紧张素Ⅱ (AngⅡ )对 β肾上腺素受体(β AR)激动剂异丙基肾上腺素 (Iso)诱导的环磷酸腺苷 (cAMP)蓄积水平的影响和激动血管紧张素Ⅱ受体 (ATR)对 β AR激动后介导的正性变力效应的影响。 方法 采用放射免疫法测定心脏cAMP、环磷酸鸟苷 (cGMP)水平 ,采用离体左心房收缩功能实验测定心脏正性变力效应。 结果 Iso刺激后 3 5月龄大鼠心脏cAMP水平明显升高〔(10 2 7± 16 9)pmol·mg心肌组织 - 1 与 (14 0 0± 2 6 7)pmol·mg心肌组织 - 1 ,P <0 0 5〕 ;AngⅡ加Iso联合刺激后 3 5月龄与 12 0月龄大鼠心脏cAMP水平均明显升高〔(10 2 7± 16 9)pmol·mg心肌组织 - 1 与 (186 5± 32 9)pmol·mg心肌组织 - 1 ,P <0 0 1;(10 4 7± 2 6 6 )pmol·mg心肌组织 - 1 与 (16 97± 4 30 )pmol·mg心肌组织 - 1 ,P <0 0 1)〕 ;Iso刺激后 3 5月龄大鼠心脏cGMP水平明显下降 ;在 3 5月龄大鼠离体左心房用 10个不同浓度的AngⅡ刺激未能诱导出正性变力效应 ;AngⅡ使 3 5月龄大鼠心脏Iso的累积浓度 收缩效应曲线左移 ,最大收缩效应增强 ,但在 12 0月龄大鼠则没有出现这种变化。 结论 AngⅡ对Iso诱导的心脏cAMP蓄积有明显的正协同作用 ;AngⅡ可增强 3 5月龄大鼠心脏 ?

Objective To study the effects of angiotensin Ⅱ(AngⅡ) on cardiac cAMP accumulative levels induced by isoprenalin(Iso) and AngⅡ on positive inotropic response induced by Iso stimulation β-adrenoceptor (β-AR) in 3.5- and 12.0- months-old rats. Methods Radioimmunoassay and functional experiment of isolated left atrias were applied to measure the levels of cAMP and cGMP and the positive inotropic response in the hearts. Results Iso increased cAMP accumulation in 3.5-month-old rats〔(1 027±169)pmol/mg vs (1 400±267)pmol/mg,P<0.05〕, and AngⅡ enhanced significantly cAMP accumulation induced by Iso in 3.5- and 12.0- months-old rats〔(1 027±169)pmol/mg vs (1 865±329)pmol/mg, P<0.01; (1 047±266)pmol/mg vs (1 697±430)pmol/mg, P<0.01, respectively〕. Iso was able to lower the cGMP levels in 3.5-month-old rats. The positive inotropic response was not induced by AngⅡ at ten different concentrations in isolated left atrias from the 3.5-month-old rats. The concentration-response-curve induced by Iso was shifted to the left significantly in the presence of AngⅡ 10 nmol/L in 3.5-month-old rats and maximum contractility was enhanced, but the concentration-response-curve for Iso was not significantly shifted in the presence of AngⅡ 10 nmol/L in 12.0-months-old rats. Conclusions AngⅡ significantly and positively synergizes toward the cAMP accumulation induced by Iso in 3.5- and 12.0-months-old rats. The positive inotropic response is not induced by AngⅡ in 3.5-month-old rats and the positive inotropic response induced by Iso is significantly enhanced by AngⅡ in 3.5-month-old rats, but it is eliminated with the increasing age.