ANGIOTENSIN-II TYPE-2 RECEPTOR INHIBITS CELL-PROLIFERATION AND ACTIVATES TYROSINE PHOSPHATASE

The angiotensin II type 2 (AT(2)) receptor inhibits basic fibroblast g rowth factor-induced proliferation of R3T3 fibroblast cells and transi ently stimulates a vanadate-sensitive phosphotyrosine phosphatase, str ongly suggesting that AT(2) is a mitogen inhibitor. We generated AT(2) gene-null mice that showed increased blood pressure, indicating the h ypotensive action of AT(2). However, inhibition of renomedullary AT(2) by selective antagonists, as reported by Sassard and associates, show that AT(2) suppresses pressure natriuresis. Thus, both AT(1) and AT(2 ) work in the direction of sodium retention, suggesting a unique role for angiotensin II in the kidney in terms of blood pressure regulation and sodium metabolism.