Opposing Actions of Angiotensin II on Microvascular Growth and Arterial Blood Pressure

Abstract

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 (AT2) 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 AT1 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 AT2 antagonism and inhibited by AT1 antagonism. Ang II infusion at a subpressor dose resulted in a pressor response with AT2 antagonism and a depressor response with AT1 antagonism. This suggests that in the microvasculature, the AT1 receptor mediates angiogenesis and vasoconstriction, and the AT2 receptor mediates an inhibition of angiogenesis and vasodilation.

Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion in revascularised syngeneic mouse islet grafts

“…Besides the well-known effects on vascular tonus, several studies implicate a role of local RAS in oxidative stress defence [33,34] and in the regulation of angiogenesis [35][36][37][38]. To evaluate the effect of islet RAS on the formation of a new islet vascular system after transplantation, losartan was, in some cases, added to the drinking water of newly transplanted animals.…”

Retinal Angiogenesis Is Mediated by an Interaction between the Angiotensin Type 2 Receptor, VEGF, and Angiopoietin

“…Angiotensin II (ANG II) has pro-angiogenic effects in various situations such as sponge implant models of angiogenesis, 34 chick chorioallantoic membrane, 35 rat cremaster muscle, 19 rat carotid artery, 36 and cornea. 37 There is evidence that the AT1 receptor mediates the proliferative effects of ANG II 7,19,38 however, the role of the AT2 receptor in these processes is less well understood with reports of pro-, anti-, and no effects on cell growth and angiogenesis.…”

“…37 There is evidence that the AT1 receptor mediates the proliferative effects of ANG II 7,19,38 however, the role of the AT2 receptor in these processes is less well understood with reports of pro-, anti-, and no effects on cell growth and angiogenesis. 9,14 -20,39,40 In the present study, we found gene expression for the AT2 receptor to be up-regulated in ROP and AT2-RB to attenuate retinal angiogenesis, indicating that the AT2 receptor promotes retinal endothelial cell growth.…”

Angiotensin II receptor pharmacology and AT1-receptor blockers

“…88 Also, coinfusion of rats with Ang II and PD 123199 results in an enhanced blood pressure response, as compared to rats infused with Ang II alone. 89 Although the AT 2 receptor seems to be involved in growth and differentiation, lack of a functional receptor still allows for development of an organism, as illustrated by the establishment of AT 2 knockout mice strains. Data obtained from these mice links the AT 2 receptor to behaviour and to altered blood pressure regulation.…”