Opposing actions of angiotensin II on microvascular growth and arterial blood pressure

We performed studies to further elucidate the mechanisms of angiotensin II (Ang II)-induced angiogenesis of the microvasculature. Rats were placed on a high salt diet (4% NaCl), and Ang II was infused at a subpressor rate (5 ng/kg per minute) for 3 days. Blood pressure was measured daily for 2 control and 3 infusion days. Microvessel density in the cremaster muscle was measured at the end of the infusion. Vessel density in rats that received subpressor Ang II infusion increased by 12.6% compared with rats that received vehicle infusion. When the angiotensin type 2 (AT(2)) receptor antagonist PD 123319 was coinfused with Ang II, blood pressure was elevated and vessel density increased above that observed with Ang II infusion alone (23% increase). When the AT(1) receptor antagonist losartan was coinfused with Ang II, blood pressure was lower than control and vessel density was reduced compared with the Ang II group but was still greater than control (7.8% increase). In this study, Ang II stimulated angiogenesis in the rat cremaster muscle; this effect was enhanced by AT(2) antagonism and inhibited by AT(1) antagonism. Ang II infusion at a subpressor dose resulted in a presser response with AT(2) antagonism and a depressor response with AT(1) antagonism. This suggests that in the microvasculature, the AT(1) receptor mediates angiogenesis and vasoconstriction, and the AT(1) receptor mediates an inhibition of angiogenesis and vasodilation.