Lancien Frédéric, Mimassi Nagi, Mabin Dominique, Le Mével Jean-Claude
LaTIM (EA 2218), INSERM U 650, Laboratoire de Neurophysiologie, Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, 22 avenue Camille Desmoulins, CS 93837, 29238, Brest Cedex 3, France.
Brain Res. 2004 May 8;1007(1-2):116-23. doi: 10.1016/j.brainres.2004.02.012.
The present study was performed in order to gain new insights into the existence of a brain renin-angiotensin system (RAS) in teleost fish. For this purpose, we investigated the effects of centrally administered angiotensin (ANG) I ([Asn(1),Val(5),Asn(9)]ANG I) and ANG II ([Asn(1),Val(5)]ANG II) on heart rate (HR) and heart rate variability (HRV) in the unanesthetized trout. The animals were studied before and after treatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor. Trout were equipped with two subcutaneous electrocardiographic electrodes and with an intracerebroventricular (i.c.v.) cannula inserted within the third ventricle of the brain. The i.c.v. injection of vehicle had no effect on the recorded parameters. The i.c.v. injections of ANG I and ANG II at doses of 5 and 50 pmol had a marked effect on HR and HRV. At a dose of 50 pmol, ANG I and ANG II produced a progressive and significant increase in HR (+36% and+45%, respectively) but elicited a profound decrease in HRV (-88% and-92%, respectively). I.c.v. injection of captopril (10 microg) had no effect on HR or HRV. However, this ACE inhibitor prevented the tachycardia and abolished the decrease in HRV mediated by 50 pmol of ANG I. In contrast, captopril had no effect upon the cardiac actions of 50 pmol of ANG II. These results give the first support for the existence of functional important ACE-like activity in the brain of a teleost fish and suggest that the brain RAS in this class of vertebrate may be involved in the control of cardiac chronotropic activity.
进行本研究是为了深入了解硬骨鱼脑中肾素-血管紧张素系统(RAS)的存在情况。为此,我们研究了向未麻醉的鳟鱼脑内注射血管紧张素(ANG)I([天冬酰胺(1),缬氨酸(5),天冬酰胺(9)]ANG I)和ANG II([天冬酰胺(1),缬氨酸(5)]ANG II)对心率(HR)和心率变异性(HRV)的影响。在使用血管紧张素转换酶(ACE)抑制剂卡托普利治疗前后对动物进行了研究。鳟鱼身上安装了两个皮下心电图电极,并在脑第三脑室内插入了一个脑室内(i.c.v.)套管。注射赋形剂对记录的参数没有影响。以5和50 pmol的剂量脑室内注射ANG I和ANG II对HR和HRV有显著影响。在50 pmol的剂量下,ANG I和ANG II使HR逐渐显著增加(分别增加36%和45%),但导致HRV显著下降(分别下降88%和92%)。脑室内注射卡托普利(10微克)对HR或HRV没有影响。然而,这种ACE抑制剂可预防心动过速,并消除由50 pmol的ANG I介导的HRV下降。相比之下,卡托普利对50 pmol的ANG II的心脏作用没有影响。这些结果首次支持了硬骨鱼脑中存在功能重要的ACE样活性,并表明这类脊椎动物的脑RAS可能参与心脏变时性活动的控制。