Modulation of vascular development and injury by angiotensin II

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 carotid artery balloon injury. Methods: AT(1) and AT(2) mRNA levels in rat aortae were measured using a quantitative reverse transcription polymerase chain reaction technique. Ang II receptor function was assessed by quantitating the effects of AT(1) (DuP753) and AT(2) (PD123319) receptor antagonists during these processes. Results: During aortic development, AT(1) expression was detected on gestational day 14, increased until embryonic day 16 (E16), after which, levels were similar throughout postnatal development. Conversely, AT(2) mRNA first appeared at E16, reached maximal levels between E19 and neonatal day 1, and decreased thereafter. DNA synthesis rates decreased 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 developmentally regulated decrease in DNA synthesis, AT(2) receptor antagonism blunted this decrease. Because activated adult medial smooth muscle cells express a neonatal phenotype after vascular injury, we assessed Ang II receptor levels 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 occurring 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 that Ang II receptors play a role in vascular development by promoting opposing effects on vascular smooth muscle cell growth. (C) 1999 Elsevier Science BN. All rights reserved.