Angiotensin II (ANG II) is increasingly recognised as a growth factor, both in its own right and through
interactions with other growth factors. There is a high density of ANG II receptors in the rat fetus,
especially the AT2 receptor, the function of which is still uncertain. We have now studied the effects of
ANG II on growth and development in the rat embryo in vitro between d 9.5 and 11.5, and characterised
the receptor subtype mediating these effects. Embryos were cultured in whole rat serum, a high molecular
weight retenate after ultrafiltration of whole rat serum, retenate with angiotensin II and retenate with ANG
II and AT1 or AT2 receptor blockers. Growth and development were scored using conventional methods.
Culture in retenate was associated with a marked reduction in growth and development by comparison with
whole rat serum. This was partly, and significantly (P<0.001), reversed by angiotensin II. The optimum
concentration of angiotensin II was found to be angiotensin II 10−11 M, within the physiological range.
Angiotensin II had highly significant effects on both somatic (P<0.001) and yolk sac/allantoic (P<0.005)
development. The latter effects suggest a role for angiotensin II in placentation. The effects of angiotensin II
were blocked by PD123319, an AT2 blocker, but not by GR117289, an AT1 blocker. Interestingly, culture
in retenate with GR117289 without added angiotensin II was also associated with some increase in growth
(P<0.05). Angiotensin II in low concentrations was measurable in the retenate, presumably arising from
the action of endogenous renin on angiotensinogen. We therefore postulate that this effect of GR117289 was
due to the action of endogenous angiotensin II on ‘uncovered’ AT2 receptors. This study has thus
demonstrated a direct growth promoting effect of angiotensin II during organogenesis in the whole rat
embryo in vitro. This effect is mediated through the AT2 receptors.