Hypovolaemia-induced vasodilatation during angiotensin AT1 receptor blockade: role of the AT2 receptor

AT1 receptor antagonists may interfere with the haemodynamic determinants of arterial pressure either directly or indirectly through the stimulation of AT2 receptor provided Ang II is available to interact with them. In order to evaluate the counteracting haemodynamic effect of AT2 receptor, a prospective, randomized, controlled experimental study was carried out in anaesthetised juvenile pigs. Pigs were randomly assigned to receive placebo (n = 6), valsartan, an AT1 receptor antagonist (a-AT1 group; n = 6), or valsartan and PD 123319, an AT2 receptor antagonist (a-AT1-2 group; n = 6) after anaesthesia and before hypovolaemia by 20% of the total estimated blood volume. Thirty minutes after bleeding, the mean arterial pressure decreased significantly and similarly in the three groups (25-30%). The placebo group had a significant decrease in cardiac output (CO) without significant change in systemic vascular resistance (SVR). Conversely, in the a-AT1 group, SVR decreased significantly with a moderate change in CO and addition of the AT2 antagonist to the AT1 antagonist (a-AT1-2 group) did not abolish the lowering in SVR. The results suggest that AT2 receptor has only a small if any contribution in the vasodilatation observed in the AT1-blockade group.