Novel Sites of Expression of Functional Angiotensin II Receptors in the Late Gestation Fetus

Abstract

In the adult, the peptide hormone angiotensin II (AII) is primarily known as a regulator of circulatory homeostasis, but recent evidence also suggests a role in cell growth. This study of AII in late gestation rat fetuses revealed the unexpected presence of receptors in skeletal muscle and connective tissue, in addition to those in recognized adult target tissues. The AII receptors in this novel location decreased by 80 percent 1 day after birth and were almost undetectable in the adult. Studies in fetal skin fibroblasts showed that the receptors were coupled to phospholipid breakdown, with concomitant increases in inositol phosphate and cytosolic calcium. The abundance, timing of expression, and unique localization of functional AII receptors in the fetus suggest a role for AII in fetal development.

Roles of mitogen-activated protein kinases and angiotensin II in renal development

“…Renal AII content is several-fold higher in newborn rats and mice than in their adult counterparts. AII receptors are also expressed to a greater extent in newborn rats (19). The mRNA for the type 1 AII receptor (AT 1 ) has been detected in the renal glomeruli of newborn rats during cell proliferation and differentiation (20).…”

“…Clinical and experimental evidence shows that the renin-angiotensin system participates in renal development (16)(17)(18)(19)(20)(21)(22). Greater angiotensinogen expression has been observed in the rat kidney during late gestation and the newborn period than in adult kidney.…”

AT1 receptor characteristics of angiotensin analogue binding in human synovium

“…These cells express both AT1 and AT2 receptors (Tsutsumi et al, 1991;Johnson & Aguilera, 1991), AT2 receptors predominating on foetal skin fibroblasts. In the rat, however, there is a dramatic decrease in angiotensin receptors on skin fibroblasts following birth (Millan et al, 1989), and in the adult rat, dermal angiotensin receptors are predominantly of the AT1 subtype (Kimura et al, 1992 (Millan et al, 1989) and their possible role in synovial hypertrophy in inflammatory arthritis deserves further investigation.…”

“…Binding of angiotensins has previously been demonstrated to microvessels in brain (Speth & Harik, 1985), retina (Ferrari-Dileo et al, 1991) and kidney (Sechi et al, 1992). In addition to effects on vascular tone and smooth muscle growth, microvascular angiotensin receptors may regulate endothelial permeability (Morel et al, 1990) and neovascularisation (Fernandez et al, 1985;Le Noble et al, 1991 (Thomas & Hoffman, 1994) and fibroblasts (Millan et al, 1989) have previously been shown to express angiotensin receptors in culture. In vitro, angiotensin inhibits macrophage migration (Weinstock & Blum, 1983) and may increase phagocytosis (Weinstock & Kassab, 1984), although the relevance of these observations to macrophage function in vivo remains uncertain.…”

The potential role of angiotensin II in the vasculature

“…The relative abundance of AT 2 subtype receptors in many fetal tissues supports a role of AT 2 during development. 16,17 Furthermore, a key role for the AT 2 subtype receptor is suggested by several studies that correlate enhanced AT 2 receptor expression with cardiovascular system disease states such as diabetes, 18 post-myocardial infarction, 19 ischaemia, 20 and hypertension, 21 eg, when cardiovascular remodelling is involved. The ability of a tissue to change the expression of AT 1 to AT 2 receptors has been described in experimentallyinduced vascular injury, 22,23 suggesting that Ang II may also play a role, through AT 2 receptors, in smooth muscle cell differentiation and proliferation.…”