Scheuer D A, Perrone M H
Rhône Poulenc Rorer Central Research, Collegeville, Pennsylvania 19426-0107.
Am J Physiol. 1993 May;264(5 Pt 2):R917-23. doi: 10.1152/ajpregu.1993.264.5.R917.
Angiotensin (ANG) can produce a biphasic arterial pressure response, i.e., an increase followed by a decrease. Because ANG type 1 (AT1) receptors mediate the pressor response to ANG, we hypothesized that the opposing depressor action is mediated by the ANG type 2 (AT2) receptors. In thiobutabarbital (Inactin)-anesthetized rats bolus injections of angiotensin III (ANG III; 100, 300, and 1,000 ng/kg iv) produced peak increases in MAP at 20 s of 13.4 +/- 1.4, 20.1 +/- 2, and 27.5 +/- 2.8 mmHg and maximum decreases in pressure at 120 s of -6.3 +/- 1.5, -6.8 +/- 2.2, and -11.4 +/- 4.9 mmHg. During blockade of the AT1 receptors with DuP 753 (losartan, 10 mg/kg) the increases in MAP were eliminated (P < 0.01), whereas the depressor responses (-24.7 +/- 8, -32.8 +/- 9.3, and -42.0 +/- 10.0 mmHg) were significantly (P < 0.05) larger. In separate groups of rats, combined blockade of both AT1 and AT2 receptors eliminated all changes in MAP in response to ANG III, whereas blockade of AT2 receptors alone enhanced the pressor response to ANG III. During AT1 receptor blockade angiotensin II also caused consistent decreases in pressure, which were inhibited during combined blockade of AT1 and AT2 receptors. Therefore, we have demonstrated that the AT2 receptors mediate a depressor response to ANG.
血管紧张素（ANG）可产生双相动脉血压反应，即先升高后降低。由于1型血管紧张素（AT1）受体介导对ANG的升压反应，我们推测相反的降压作用是由2型血管紧张素（AT2）受体介导的。在硫喷妥巴比妥（因钠）麻醉的大鼠中，静脉推注血管紧张素III（ANG III；100、300和1000 ng/kg）后，平均动脉压（MAP）在20秒时峰值升高分别为13.4±1.4、20.1±2和27.5±2.8 mmHg，在120秒时压力最大降低分别为-6.3±1.5、-6.8±2.2和-11.4±4.9 mmHg。在用杜普753（氯沙坦，10 mg/kg）阻断AT1受体期间，MAP的升高被消除（P<0.01），而降压反应（-24.7±8、-32.8±9.3和-42.0±10.0 mmHg）显著（P<0.05）增大。在另一组大鼠中，同时阻断AT1和AT2受体可消除对ANG III的MAP所有变化，而单独阻断AT2受体则增强对ANG III的升压反应。在阻断AT1受体期间，血管紧张素II也导致血压持续降低，在同时阻断AT1和AT2受体期间这种降低受到抑制。因此，我们证明了AT2受体介导对ANG的降压反应。
