Role of AT2 receptors in the cardiovascular events following microinjection of angiotensin II into the superior colliculus of anaesthetised rats.
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.
D'Amico
M
M
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery 2nd University of Naples, Italy.
Di Filippo
C
C
Rossi
F
F
Warner
T D
TD
D000768:Anesthesia, General; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008863:Microspheres; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013477:Superior Colliculi / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan