Role of AT2 receptors in the cardiovascular events following microinjection of angiotensin II into the superior colliculus of anaesthetised rats

Abstract

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 10 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.