THE ANGIOTENSIN-II TYPE-2 (AT(2)) RECEPTOR ANTAGONIZES THE GROWTH EFFECTS OF THE AT(1) RECEPTOR - GAIN-OF-FUNCTION STUDY USING GENE-TRANSFER

The type 1 angiotensin II (AT(1)) receptor is well characterized but the type 2 (AT(2)) receptor remains an enigma. We tested the hypothesis that the AT(2) receptor can modulate the growth of vascular smooth muscle cells by transfecting an AT(2) receptor expression vector into the balloon-injured rat carotid artery and observed that overexpression of the AT(2) receptor attenuated neointimal formation. In cultured smooth muscle cells, AT(2) receptor transfection reduced proliferation and inhibited mitogen-activated protein kinase activity. Furthermore, we demonstrated that the AT(2) receptor mediated the developmentally regulated decrease in aortic DNA synthesis at the latter stages of gestation. These results suggest that the AT(2) receptor exerts an antiproliferative effect, counteracting the growth action of AT(1) receptor.