ROLE OF AT(2) RECEPTORS IN THE CARDIOVASCULAR EVENTS FOLLOWING MICROINJECTION OF ANGIOTENSIN-II INTO THE SUPERIOR COLLICULUS OF ANESTHETIZED RATS

Central injection of angiotensin II (ANGII) induces presser and region al haemodynamic effects. Here we have investigated the systemic and re gional cardiovascular changes induced by injection of ANGII into the s uperficial layer of the superior colliculus (SC) of male rats anaesthe tised with urethane. In addition, we have used the AT(1) receptor-sele ctive antagonist, losartan, and the AT(2) receptor-selective antagonis t, PD123319 to characterise the receptor(s) mediating these effects. I njection 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 mann er, 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 incre ases in blood pressure induced by ANGII(I nmol; 43 +/- 6 mmHg, It = 5) were greatly reduced (> 85%) by pre-administration to the SC of PD123 319 (50 nmol/rat), but were unaffected by losartan (50 nmol/rat). Simi larly, PD123319 prevented the decrease in heart rate induced by ANGII while losartan did not affect it. Injection of ANGII (1 nmol) also inc reased (P < 0.01) total peripheral resistance (TPR; control, 2.36 +/- 0.1 mmHg ml(-1) min 100 g body weight) by 130 +/- 10% (it = 5) and red uced the cardiac output (GO; control, 99.8 +/- 1.3 mi 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 o rgans, such as the left and light kidney (390 +/- 15%, P < 0.01 and 35 2 +/- 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 increase s in TPR and vascular resistance, and the reduction in CO caused by AN GII. Losartan did not affect the responses to ANGII. Thus, injection o f ANGII into the SC causes complex haemodynamic changes which are sens itive to AT(2) receptor antagonism. AT(2) receptors are, therefore, th e predominant mediators of the actions of ANGII into the superior coll iculus of the rat.