Objective: To examine the exact profile of expression and to determine the
functional significance of the angiotensin II (Ang II), type 1 (AT(1)) and
type 2 (AT(2)) receptors during rat aortic development and following rat ca
rotid artery balloon injury. Methods: AT(1) and AT(2) mRNA levels in rat ao
rtae were measured using a quantitative reverse transcription polymerase ch
ain reaction technique. Ang II receptor function was assessed by quantitati
ng the effects of AT(1) (DuP753) and AT(2) (PD123319) receptor antagonists
during these processes. Results: During aortic development, AT(1) expressio
n was detected on gestational day 14, increased until embryonic day 16 (E16
), after which, levels were similar throughout postnatal development. Conve
rsely, AT(2) mRNA first appeared at E16, reached maximal levels between E19
and neonatal day 1, and decreased thereafter. DNA synthesis rates decrease
d with aortic development (high at E15, 73.8+/-3.1%; dropping to 37.5+/-2.3
% by E21). Whereas AT(1) receptor antagonism accelerated this developmental
ly regulated decrease in DNA synthesis, AT(2) receptor antagonism blunted t
his decrease. Because activated adult medial smooth muscle cells express a
neonatal phenotype after vascular injury, we assessed Ang II receptor level
s and function after carotid artery balloon injury. Both receptor subtypes
increased; however, AT(2) receptor mRNA expression peaked earlier than AT(1
) (48 to 72 h after injury). As with aortic development, DNA synthesis occu
rring between 24 to 48 h after injury (when AT(1) receptors constitute 10%
of the Ang II receptor population) decreased in DuP753-treated animals and
increased in PD123319-treated animals. Conclusion: These results indicate t
hat Ang II receptors play a role in vascular development by promoting oppos
ing effects on vascular smooth muscle cell growth. (C) 1999 Elsevier Scienc
e BN. All rights reserved.