Szczepańska-Sadowska E, Paczwa P, Loń S, Ganten D
Department of Clinical and Applied Physiology, the Medical University of Warsaw, Poland.
J Hypertens. 1998 Oct;16(10):1505-14. doi: 10.1097/00004872-199816100-00016.
Renin transgenic hypertensive rats [TGR(mRen2)27] have increased contents of angiotensin II and arginine vasopressin (AVP) in the cardiovascular brain regions. The aim of the present study was to evaluate the effects of centrally released AVP on the regulation of baseline blood pressure in TGR(mRen2)27 rats and to determine the interaction between AVP and angiotensin II in the central control of blood pressure in this model of hypertension.
Three basic series of experiments were performed on 20 TGR(mRen2)27 and 20 Hannover Sprague-Dawley conscious rats, chronically instrumented with lateral cerebral ventricle (LCV) cannulae and femoral artery catheters. In series 1, blood pressure and heart rate were recorded during an LCV infusion of artificial cerebrospinal fluid before and after LCV administration of angiotensin II. In series 2, the effects of an LCV administration of angiotensin 11 (100 ng) on mean arterial pressure and the heart rate were determined during LCV infusion of a selective AVP receptor (V1) antagonist [1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine vasopressin (MeCAAVP) and d(CH2)5[Tyr(Me)2,Ala-NH2(9)]AVP] or a selective angiotensin II type 1 (AT1) receptor antagonist (losartan) or both. In series 3, mean arterial pressure and the heart rate were determined after an LCV injection of either AVP (10 ng) or AVP together with angiotensin II.
The LCV infusions of antagonists to V1 and AT1 receptors caused significant comparable decreases in baseline MAP in TGR(mRen2)27 but not in Sprague-Dawley rats. Angiotensin II elicited significant pressor responses, both in TGR(mRen2)27 and in Sprague-Dawley rats. Blockade of V1 receptors significantly reduced the duration and the maximum amplitude of the central pressor response to angiotensin II in TGR(mRen2)27 rats, whereas in Sprague-Dawley rats the maximum pressor effect was not significantly altered. In both strains, the pressor response to angiotensin II was abolished by blockade of AT1 receptors.
The results indicate that the elevated blood pressure in TGR(mRen2)27 rats is partly caused by increased function of the brain angiotensinergic AT1 and vasopressinergic V1 systems. Centrally released AVP is involved in mediation of the pressor effect exerted by centrally applied angiotensin II in TGR(mRen2)27 rats.
肾素转基因高血压大鼠[TGR(mRen2)27]心血管脑区的血管紧张素II和精氨酸加压素(AVP)含量增加。本研究的目的是评估中枢释放的AVP对TGR(mRen2)27大鼠基线血压调节的影响，并确定在该高血压模型中AVP与血管紧张素II在血压中枢控制中的相互作用。
对20只TGR(mRen2)27大鼠和20只汉诺威Sprague-Dawley清醒大鼠进行了三个基本系列的实验，这些大鼠长期植入侧脑室(LCV)套管和股动脉导管。在系列1中，在侧脑室注射血管紧张素II前后，通过侧脑室输注人工脑脊液记录血压和心率。在系列2中，在侧脑室输注选择性AVP受体(V1)拮抗剂[1-(1-巯基-4-甲基环己烷乙酸)-8-精氨酸加压素(MeCAAVP)和d(CH2)5[Tyr(Me)2,Ala-NH2(9)]AVP]或选择性血管紧张素II 1型(AT1)受体拮抗剂(氯沙坦)或两者的情况下，测定侧脑室注射血管紧张素II(100 ng)对平均动脉压和心率的影响。在系列3中，在侧脑室注射AVP(10 ng)或AVP与血管紧张素II联合注射后，测定平均动脉压和心率。
侧脑室注射V1和AT1受体拮抗剂可使TGR(mRen2)27大鼠的基线平均动脉压显著降低，但对Sprague-Dawley大鼠无此作用。血管紧张素II在TGR(mRen2)27大鼠和Sprague-Dawley大鼠中均引起显著的升压反应。阻断V1受体可显著缩短TGR(mRen2)27大鼠对血管紧张素II的中枢升压反应的持续时间并降低其最大幅度，而在Sprague-Dawley大鼠中，最大升压效应无显著改变。在两种品系中，阻断AT1受体均可消除对血管紧张素II的升压反应。
结果表明，TGR(mRen2)27大鼠血压升高部分是由于脑内血管紧张素能AT1和加压素能V1系统功能增强所致。中枢释放的AVP参与介导中枢应用血管紧张素II对TGR(mRen2)27大鼠产生的升压作用。
