Increased vasoconstrictor response of the mouse lacking angiotensin II type 2 receptor

The angiotensin II (Ang II) type 1 receptor mediates various actions of Ang II, whereas the function of the type 2 (AT2) receptor is not well understo od. In the mice lacking the gene encoding the AT2 receptor, the presser res ponse to Ang II was increased although the underlying mechanism is unknown. We tested the hypothesis that vasoconstrictor response is exaggerated in t he AT2 receptor null mice. We measured hemodynamic parameters and evaluated systemic vascular resistance (SVR) in the anesthetized open-chest wildtype and AT2 receptor null mice. Ang II infusion caused dose-dependent increase s in SVR in both strains, while the response was significantly higher at 0. 5 mu g/kg Ang II in the AT2 receptor null mice (305 +/- 53% of baseline) th an in the wild-type mice (179 +/- 27% of baseline). To investigate further the vascular contractility, we examined contraction of aortic rings in vitr o. The contraction induced by 1 ELM Ang II was increased in the AT2 recepto r null mice compared with that in the wild-type mice (0.82 +/- 0.11 vs. 0.5 4 a 0.12 g), Ang II-induced contraction was still greater in the AT2 recept or null mice when calibrated by the maximum tension induced by 90 mM KCl. T hese data suggest that the AT2 receptor modulates vascular contractility, w hich may influence blood pressure. (C) 1999 Academic Press.