No vasoactive role of the angiotensin II type 2 receptor in normotensive Wistar rats.
OBJECTIVE
To investigate the vasoactive consequences of angiotensin II type 2 receptor stimulation in vivo.


METHODS
Three consecutive 10 min intravenous infusions of angiotensin (Ang) II (100, 300 and 1000 ng/kg per min) were given to 20 pentobarbitone-anaesthetized normotensive Wistar rats (weight 330+/-6 g, mean +/- SEM). The rats had been pretreated with saline (n = 8), the angiotensin II type 1 receptor antagonist, irbesartan (100 microg/kg per min for 30 min, n = 6), or the angiotensin II type 2 receptor antagonist, PD123319 (20 microg/kg per min for 30 min followed by continuous infusion throughout the entire experiment, n = 6). Regional haemodynamic effects of Ang II were studied using the radioactive microsphere method.


RESULTS
Ang II increased mean arterial blood pressure (MAP) and heart rate by, maximally, 44+/-9 and 26+/-6%, respectively (P < 0.05 compared with baseline), and decreased cardiac output and systemic vascular conductance (cardiac output/MAP) by, maximally, 24+/-8 and 47+/-4%, respectively (P < 0.05 compared with baseline). The Ang II-induced decrease in systemic vascular conductance was caused by decreases in vascular conductances (regional flow/MAP) of the gastrointestinal tract (52+/-4%), kidney (63+/-3%), skeletal muscle (39+/-8%), skin (63+/-4%), mesentery + pancreas (32+/-11%), adrenal (27+/-11%) and spleen (57+/-6%) (all P < 0.05 compared with baseline). Irbesartan increased baseline vascular conductances in adrenal, brain and kidney, and inhibited all haemodynamic responses induced by Ang II. PD123319 affected neither baseline values nor the Ang II-induced haemodynamic responses.


CONCLUSIONS
Ang II-induced systemic and regional haemodynamic effects in normotensive Wistar rats are mediated exclusively via angiotensin II type 1 receptors. No evidence for angiotensin II type 2 receptor-mediated vasoactive responses was obtained.
Schuijt
M P
MP
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
de Vries
R
R
Saxena
P R
PR
Danser
A H
AH
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D000077405:Irbesartan; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D012016:Reference Values; D013777:Tetrazoles / Q000494:pharmacology; D014666:Vasomotor System / Q000502:physiology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C073402:PD 123319; D000077405:Irbesartan