Moura André Luiz de, Hyslop Stephen, Grassi-Kassisse Dora M, Spadari Regina C
a Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos, SP, Brazil.
b Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Can J Physiol Pharmacol. 2017 Sep;95(9):999-1008. doi: 10.1139/cjpp-2016-0622. Epub 2017 Apr 30.
Altered sensitivity to the chronotropic effect of catecholamines and a reduction in the β/β-adrenoceptor ratio have previously been reported in right atria of stressed rats, human failing heart, and aging. In this report, we investigated whether left atrial inotropism was affected by foot-shock stress. Male rats were submitted to 3 foot-shock sessions and the left atrial inotropic response, adenylyl cyclase activity, and β-adrenoceptor expression were investigated. Left atria of stressed rats were supersensitive to isoprenaline when compared with control rats and this effect was abolished by ICI118,551, a selective β-receptor antagonist. Schild plot slopes for the antagonism between CGP20712A (a selective β-receptor antagonist) and isoprenaline differed from unity in atria of stressed but not control rats. Atrial sensitivity to norepinephrine, as well as basal and forskolin- or isoprenaline-stimulated adenylyl cyclase activities were not altered by stress. The effect of isoprenaline on adenylyl cyclase stimulation was partially blocked by ICI118,551 in atrial membranes of stressed rats. These findings indicate that foot-shock stress equally affects inotropism and chronotropism and that β-adrenoceptor upregulation contributes to the enhanced inotropic response to isoprenaline.
先前已有报道称,应激大鼠的右心房、人类衰竭心脏以及衰老过程中,对儿茶酚胺变时作用的敏感性发生改变,且β/β-肾上腺素能受体比例降低。在本报告中,我们研究了足部电击应激是否会影响左心房的变力性。将雄性大鼠进行3次足部电击实验,并对其左心房的变力性反应、腺苷酸环化酶活性和β-肾上腺素能受体表达进行研究。与对照大鼠相比,应激大鼠的左心房对异丙肾上腺素超敏,且这种效应被选择性β受体拮抗剂ICI118,551消除。在应激大鼠而非对照大鼠的心房中,CGP20712A(一种选择性β受体拮抗剂)与异丙肾上腺素之间拮抗作用的希尔德图斜率不同于1。应激并未改变心房对去甲肾上腺素的敏感性,以及基础和福斯高林或异丙肾上腺素刺激的腺苷酸环化酶活性。在应激大鼠的心房膜中,异丙肾上腺素对腺苷酸环化酶刺激的作用被ICI118,551部分阻断。这些发现表明,足部电击应激同样会影响变力性和变时性,且β-肾上腺素能受体上调有助于增强对异丙肾上腺素的变力性反应。