Chen Yanfang, Chen Hao, Morris Mariana
Department of Pharmacology and Taxicology, 3640 Colonel Glenn Highway, Wright State University School of Medicine, Dayton, OH 45435-0001, USA.
Exp Physiol. 2005 Sep;90(5):739-46. doi: 10.1113/expphysiol.2005.030643. Epub 2005 Jun 8.
Experiments were performed to study the role of angiotensin (Ang) AT1a and AT1b receptor subtypes in osmotic regulation of blood pressure using gene deletion and pharmacological methods. The cardiovascular effects of hypertonic saline (HS) or vasopressin (VP) delivered via vascular catheters were measured in Ang AT1a gene deletion (AT1a-/-) and control (AT1a+/+) mice. Blood pressure (BP) and heart rate (HR) were recorded in conscious mice using direct carotid catheters. Plasma osmolality and VP concentration were also measured. The major finding was that deletion of AT1a receptors resulted in enhanced BP response to osmotic stimulation. This was seen after acute HS injection (20 microl, 20% NaCl). The peak percentage change in mean arterial pressure (MAP) was 15.4+/-1.9% versus 28.1+/-2.4% (AT1a+/+versus AT1a-/-, respectively). Losartan (AT1 antagonist), but not PD123319 (AT2 antagonist), inhibited the HS-induced MAP response, specifically in AT1a-/- mice. Plasma osmolality and VP concentration were elevated after HS injection with no differences noted between groups. Vascular injection of VP (5 ng g-1) increased BP and HR, with similar MAP response between groups. Evidence shows that removal of Ang AT1a receptors results in a significant enhancement in the pressor response to acute osmotic stimulation. Studies of AT1 receptor blockade indicate that complementary Ang AT1b receptors, but not AT2 receptors, may be involved in the osmotic response.
采用基因敲除和药理学方法进行实验，以研究血管紧张素（Ang）AT1a和AT1b受体亚型在血压渗透压调节中的作用。在血管紧张素AT1a基因敲除（AT1a-/-）小鼠和对照（AT1a+/+）小鼠中，测量经血管导管输注高渗盐水（HS）或血管加压素（VP）后的心血管效应。使用直接颈动脉导管记录清醒小鼠的血压（BP）和心率（HR）。还测量了血浆渗透压和VP浓度。主要发现是，敲除AT1a受体会增强对渗透压刺激的血压反应。这在急性注射HS（20微升，20%氯化钠）后可见。平均动脉压（MAP）的峰值百分比变化分别为15.4±1.9%和28.1±2.4%（分别为AT1a+/+和AT1a-/-）。氯沙坦（AT1拮抗剂）而非PD123319（AT2拮抗剂）抑制了HS诱导的MAP反应，特别是在AT1a-/-小鼠中。注射HS后血浆渗透压和VP浓度升高，各组之间无差异。血管内注射VP（5纳克/克-1）可升高BP和HR，各组之间的MAP反应相似。有证据表明，去除Ang AT1a受体会导致对急性渗透压刺激的升压反应显著增强。对AT1受体阻断的研究表明，互补的Ang AT1b受体而非AT2受体可能参与渗透压反应。
