D'Amico M, Di Filippo C, Rossi F, Warner T D
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery 2nd University of Naples, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Feb;357(2):121-5. doi: 10.1007/pl00005145.
Central injection of angiotensin II (ANGII) induces pressor and regional haemodynamic effects. Here we have investigated the systemic and regional cardiovascular changes induced by injection of ANGII into the superficial layer of the superior colliculus (SC) of male rats anaesthetised with urethane. In addition, we have used the AT1 receptor-selective antagonist, losartan, and the AT2 receptor-selective antagonist, PD123319 to characterise the receptor(s) mediating these effects. Injection of ANGII (0.1, 1 and 100 nmol/rat) into the superficial layer of the SC significantly (P < 0.05) increased, in a dose-dependent manner, the mean arterial blood pressure (MAP) while decreasing the heart rate, (e.g. by 37+/-4 beats min(-1), at 1 nmol, P < 0.05). The increases in blood pressure induced by ANGII (1 nmol; 43+/-6 mmHg, n = 5) were greatly reduced (> 85%) by pre-administration to the SC of PD123319 (50 nmol/rat), but were unaffected by losartan (50 nmol/rat). Similarly, PD123319 prevented the decrease in heart rate induced by ANGII while losartan did not affect it. Injection of ANGII (1 nmol) also increased (P < 0.01) total peripheral resistance (TPR; control, 2.36+/-0.1 mmHg ml(-1) min 100 g body weight) by 130+/-10% (n = 5) and reduced the cardiac output (CO; control, 99.8+/-1.3 ml min[-1]) by 51+/-3% (n = 5), as determined by radioactive microspheres. The increase in TPR was associated with increases in the vascular resistances of organs, such as the left and right kidney (390+/-15%, P < 0.01 and 352+/-12%, P < 0.01 respectively), the skeletal muscle (91+/-7%, P < 0.05, n = 5), the stomach (43+/-2%, P < 0.01, n = 5), the colon (50+/-3%, P < 0.05, n = 5) and the caecum (65+/-5%, P < 0.05, n = 5). Pre-treatment of the SC with PD123319 reduced (P < 0.01) the increases in TPR and vascular resistance, and the reduction in CO caused by ANGII. Losartan did not affect the responses to ANGII. Thus, injection of ANGII into the SC causes complex haemodynamic changes which are sensitive to AT2 receptor antagonism. AT2 receptors are, therefore, the predominant mediators of the actions of ANGII into the superior colliculus of the rat.
向中枢注射血管紧张素II（ANGII）可诱导升压及局部血流动力学效应。在此，我们研究了向用乌拉坦麻醉的雄性大鼠上丘（SC）表层注射ANGII所引起的全身及局部心血管变化。此外，我们使用了AT1受体选择性拮抗剂氯沙坦以及AT2受体选择性拮抗剂PD123319来确定介导这些效应的受体。向SC表层注射ANGII（0.1、1和100 nmol/只大鼠）可显著（P<0.05）且呈剂量依赖性地升高平均动脉血压（MAP），同时降低心率（例如，1 nmol时降低37±4次/分钟，P<0.05）。ANGII（1 nmol；43±6 mmHg，n = 5）引起的血压升高在预先向SC注射PD123319（50 nmol/只大鼠）后大幅降低（>85%），但不受氯沙坦（50 nmol/只大鼠）影响。同样，PD123319可防止ANGII引起的心率降低，而氯沙坦对此无影响。注射ANGII（1 nmol）还使总外周阻力（TPR；对照组，2.36±0.1 mmHg·ml⁻¹·min⁻¹·100 g体重）增加（P<0.01）130±10%（n = 5），并使心输出量（CO；对照组，99.8±1.3 ml·min⁻¹）降低51±3%（n = 5），这是通过放射性微球测定的。TPR的增加与各器官血管阻力的增加相关，如左、右肾（分别为390±15%，P<0.01和352±12%，P<0.01）、骨骼肌（91±7%，P<0.05，n = 5）、胃（43±2%，P<0.01，n = 5）、结肠（50±3%，P<0.05，n = 5）和盲肠（65±5%，P<0.05，n = 5）。预先用PD123319处理SC可降低（P<0.01）ANGII引起的TPR和血管阻力增加以及CO降低。氯沙坦不影响对ANGII的反应。因此，向SC注射ANGII会引起复杂的血流动力学变化，这些变化对AT2受体拮抗敏感。所以，AT2受体是ANGII作用于大鼠上丘的主要介导者。
