© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Modulation of vascular development and injury by angiotensin II
aFalk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA
bMedical Affairs, Zeneca Pharmaceuticals, 1800 Concord Pike, PO Box 15437, Wilmington, DE 19850, USA
cDepartment of Pharmacology, University of Wuerzburg, Versbacher Strasse 9, 97078, Wuerzburg, Germany
dStanford University School of Medicine, VA Palo Alto Health Care System, 38081 Miranda Avenue, Palo Alto, CA 94304, USA
eLaboratory of Genetic Physiology, Brigham and Women’s Hospital, Thorn-13, 75 Francis Street, Boston, MA 02115, USA
* Corresponding author. Laboratory of Genetic Physiology, Brigham and Women’s Hospital, Thorn-13, 75 Francis Street, Boston, MA 02115, USA. Tel.: +1-617-732-8799; fax: +1-617-975-0995; e-mail: rpratt@bustoff.bwh.harvard.edu
Objective: To examine the exact profile of expression and to determine the functional significance of the angiotensin II (Ang II), type 1 (AT1) and type 2 (AT2) receptors during rat aortic development and following rat carotid artery balloon injury. Methods: AT1 and AT2 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 AT1 (DuP753) and AT2 (PD123319) receptor antagonists during these processes. Results: During aortic development, AT1 expression was detected on gestational day 14, increased until embryonic day 16 (E16), after which, levels were similar throughout postnatal development. Conversely, AT2 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 AT1 receptor antagonism accelerated this developmentally regulated decrease in DNA synthesis, AT2 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, AT2 receptor mRNA expression peaked earlier than AT1 (48 to 72 h after injury). As with aortic development, DNA synthesis occurring between 24 to 48 h after injury (when AT2 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.
KEYWORDS Protein coupled receptors; Quantitative RT-PCR; Neointima; Developmental biology; Smooth muscle; Growth control
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