Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II–Infused Rats

Abstract

Angiotensin II plays an important role in vascular remodeling through effects that involve, in part, interactions of vascular smooth muscle cells with extracellular matrix via integrins, which belong to a family of transmembrane receptors. We hypothesized that angiotensin (Ang) II regulates expression of vascular integrins and their ligands in experimental hypertension. Rats were infused subcutaneously with Ang II and received angiotensin type-1 (AT 1 ) receptor blocker losartan, the AT 1 /angiotensin type-2 (AT 2 ) [Sar 1 -Ile 8 ]-Ang II, or the vasodilator hydralazine for 7 days. Osteopontin and integrin subunit expression were evaluated immunohistochemically. Ang II enhanced vascular α 8 , β 1 , β 3 integrins and osteopontin expression, which were significantly reduced by losartan, [Sar 1 -Ile 8 ]-Ang II, and hydralazine. Although Ang II increased vascular α 5 subunit expression, this was additionally increased by losartan. Losartan was the only treatment that induced α 1 subunit expression. These results demonstrate that AT 1 and AT 2 receptors have countervailing effects on vascular integrin subunit expression that may influence their effects on vascular remodeling and extracellular matrix composition.