Submitted on June 13, 2006
Accepted on March 22, 2007
Blockade of both 
1A- and 1B -adrenergic receptor-subtype signaling is required to inhibit neointimal formation in the mouse femoral artery
Chihiro Hosoda1, Masami Hiroyama2, Atsushi Sanbe2, Jyun-ichi Birumachi2, Tadaichi Kitamura3, Susanna Cotecchia4, Paul C Simpson5, Gozoh Tsujimoto6, and Akito Tanoue7*
1 Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan; Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
2 Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan
3 Department of Urology, Faculty of Medicine, University of Tokyo, Tokyo, Japan
4 Institut de Pharmacologie et Toxicologie, Universit de Lausanne, Lausanne, Switzerland
5 Cardiology Division, San Francisco Veterans Affairs Medical Center, and the Cardiovascular Research Institute and Department of Medicine, University, San Francisco, California, United States
6 Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, United States
7 Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: atanoue{at}nch.go.jp.
Attenuation of early restenosis after percutaneus coronary intervention (PCI) is important for the successful treatment of coronary artery disease. Some clinical studies have shown that hypertension is a risk factor for early restenosis after PCI. These findings suggest that 
1-adrenergic receptors (1-ARs) may facilitate restenosis after PCI because of 1-AR's remarkable contribution to the onset of hypertension. In this study, we examined the neointimal formation after vascular injury in the femoral artery of 1A-knockout (1A-KO), 1B-knockout (1B-KO), 1D-knockout (1D-KO), 1A-/1B-AR double-knockout (1AB-KO), and wild-type (WT) mice to investigate the functional role of each 1-AR subtype in neointimal formation, which is known to promote restenosis. Neointimal formation four weeks after wire injury was significantly (p < 0.05) smaller in 1AB-KO mice than in any other group of mice, while blood pressures were not altered in any of the groups of mice after wire injury compared to those before it. These results suggest that lack of both 1A-　and 1B-ARs could be necessary to inhibit neointimal formation in the mouse femoral artery.
