Böhm M, Beuckelmann D, Diet F, Feiler G, Lohse M J, Erdmann E
Medizinische Klinik I, Universität München, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Oct;338(4):383-91. doi: 10.1007/BF00172114.
The effects of isoprenaline, Ca2+ and phenylephrine (in the presence of propranolol) on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched (14-18 weeks) Wistar Kyoto control rats (WK). Cardiac alpha- and beta-adrenoceptors were characterized by radioligand binding studies. The positive inotropic effect of isoprenaline in SHR was less effective than in control rats. The EC50 values did not differ in both groups. In SHR, isoprenaline was less effective than Ca2+ to increase force of contraction whereas in WK it had the same effectiveness as Ca2+. The positive inotropic effect of phenylephrine in the presence of propranolol was similar in SHR and WK. In SHR, both the densities of cardiac alpha- and beta-adrenoceptors were reduced. In beta-adrenoceptor binding experiments, the nonhydrolysable GTP analog Gpp(NH)p caused a rightward shift of agonist competition curves of isoprenaline. Biphasic competition curves revealed a similar percentage of low and high affinity sites in SHR and WK, respectively. In alpha-adrenoceptor binding experiments, Gpp(NH)p caused no detectable shift of agonist competition curves with norepinephrine. It is suggested that cardiac beta-adrenoceptor down-regulation is involved in the reduced positive inotropic effect of isoprenaline in SHR. Functional uncoupling of beta-adrenoceptors does not appear to be involved in the reduced beta-adrenoceptor-mediated positive inotropism in SHR. Binding studies do not show evidence for a large number of alpha-adrenoceptors coupling to a guanine-nucleotide binding protein in the rat heart. Finally, in ventricular myocardium of SHR, cardiac alpha-adrenoceptors do not serve as a reserve mechanism during impaired beta-adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了异丙肾上腺素、Ca²⁺和去氧肾上腺素（在普萘洛尔存在下）对自发性高血压大鼠（SHR）和年龄匹配（14 - 18周）的Wistar Kyoto对照大鼠（WK）离体电驱动乳头肌收缩力的影响。通过放射性配体结合研究对心脏α和β肾上腺素能受体进行了表征。异丙肾上腺素对SHR的正性肌力作用比对对照大鼠的作用效果差。两组的半数有效浓度（EC50）值无差异。在SHR中，异丙肾上腺素增加收缩力的效果不如Ca²⁺，而在WK中其效果与Ca²⁺相同。去氧肾上腺素在普萘洛尔存在下的正性肌力作用在SHR和WK中相似。在SHR中，心脏α和β肾上腺素能受体的密度均降低。在β肾上腺素能受体结合实验中，不可水解的鸟苷三磷酸类似物Gpp(NH)p使异丙肾上腺素的激动剂竞争曲线向右移动。双相竞争曲线分别显示SHR和WK中低亲和力和高亲和力位点的百分比相似。在α肾上腺素能受体结合实验中，Gpp(NH)p未引起去甲肾上腺素激动剂竞争曲线的可检测移动。提示心脏β肾上腺素能受体下调参与了SHR中异丙肾上腺素正性肌力作用减弱的过程。β肾上腺素能受体的功能解偶联似乎不参与SHR中β肾上腺素能受体介导的正性肌力作用减弱。结合研究未显示大鼠心脏中大量α肾上腺素能受体与鸟嘌呤核苷酸结合蛋白偶联的证据。最后，在SHR的心室心肌中，心脏α肾上腺素能受体在β肾上腺素能刺激受损时不作为储备机制。（摘要截短于250字）
