Growth-dependent induction of angiotensin II type 2 receptor in rat mesangial cells

Angiotensin II acts on at least two receptor subtypes, AT(1) and AT(2). Although the physiological role of the AT(2) receptor is still poorly de fined, it may be implicated in inhibition of cell growth, vasorelaxation, and apoptosis. In the present study, to investigate the role of the AT(2) receptor in the kidney and its implication in hypertensive stales, we examined its expression using cultured mesangial cells (MC) from normotensive Wistar-Kyoto rats (WKY) and from stroke-prone spontaneously hypertensive rats (SHRSP). Receptor binding assays were performed using a nonselective ligand, [Sar(1),Ile(8)]angiotensin II, or AT(2)-selective CGP42112A. Binding assays revealed that MC from WKY exhibited both AT(1) and AT(2) receptors, the ratio of which was confluence-dependent. In contrast, MC from SHRSP, whose proliferation activity was much higher than those from WKY, showed only the AT(1) subtype. In receptor binding and Northern blot analyses, expression of the AT(2) receptor of WKY-MC was low in the growing state but significantly induced upon confluence to become abundant in the post confluent state, whereas that of SHRSP-MC was undetectable in either state. Gene expressions of AT(1A) and AT(1B) receptors were not significantly altered in either strain during the time in culture. These results indicate that the mesangial AT(2)-receptor expression is growth-dependent and suggest a role in the inhibition of MC growth in WKY. Much lower expression of the AT(2) receptor in MC from SHRSP may suggest involvement in their higher proliferation activity and possibly in consequent renal disorders.