Worck R H, Staahltoft D, Jonassen T E, Frandsen E, Ibsen H, Petersen J S
Department of Pharmacology, The Panum Institute Bldg. 18.6, University of Copenhagen, Blegdamsvej. 3, DK-2200 Copenhagen N, Denmark.
Am J Physiol Regul Integr Comp Physiol. 2001 Apr;280(4):R1162-8. doi: 10.1152/ajpregu.2001.280.4.R1162.
Simultaneous blockade of systemic AT1 and AT2 receptors or converting enzyme inhibition (CEI) attenuates the hypoglycemia-induced reflex increase of epinephrine (Epi). To examine the role of brain AT1 and AT2 receptors in the reflex regulation of Epi release, we measured catecholamines, hemodynamics, and renin during insulin-induced hypoglycemia in conscious rats pretreated intracerebroventricularly with losartan, PD-123319, losartan and PD-123319, or vehicle. Epi and norepinephrine (NE) increased 60-and 3-fold, respectively. However, the gain of the reflex increase in plasma Epi (Deltaplasma Epi/Deltaplasma glucose) and the overall Epi and NE responses were similar in all groups. The ensuing blood pressure response was similar between groups, but the corresponding bradycardia was augmented after PD-123319 (P < 0.05 vs. vehicle) or combined losartan and PD-123319 (P < 0.01 vs. vehicle). The findings indicate 1) brain angiotensin receptors are not essential for the reflex regulation of Epi release during hypoglycemia and 2) the gain of baroreceptor-mediated bradycardia is increased by blockade of brain AT2 receptors in this model.
同时阻断全身的AT1和AT2受体或抑制转化酶（CEI）可减弱低血糖诱导的肾上腺素（Epi）反射性增加。为了研究脑内AT1和AT2受体在Epi释放反射调节中的作用，我们在清醒大鼠中，通过脑室内注射氯沙坦、PD - 123319、氯沙坦和PD - 123319或赋形剂进行预处理后，测量胰岛素诱导低血糖期间的儿茶酚胺、血流动力学和肾素。Epi和去甲肾上腺素（NE）分别增加了60倍和3倍。然而，所有组血浆Epi反射性增加的增益（Δ血浆Epi/Δ血浆葡萄糖）以及总的Epi和NE反应相似。随后的血压反应在各组之间相似，但在注射PD - 123319后（与赋形剂组相比，P < 0.05）或联合注射氯沙坦和PD - 123319后（与赋形剂组相比，P < 0.01）相应的心动过缓加剧。这些发现表明：1）脑内血管紧张素受体对低血糖期间Epi释放的反射调节并非必不可少；2）在该模型中，阻断脑内AT2受体可增加压力感受器介导的心动过缓的增益。
