Proangiogenic Effects of α1-Adrenergic Receptor Blockade.

Authors :: Iaccarino, Guido
Ciccarelli, Michele
Santulli, Gaetano
Campanile, Alfonso
Galasso, Gennaro
Cervero, Pasquale
Altobelli, Giuseppina
Cimini, Vincenzo
Piscione, Federico
Trimarco, Bruno
Source :: FASEB Journal; Apr2007, Vol. 21 Issue 6, pA1212-A1213, 2p, 1 Chart
Publication Year :: 2007
Abstract: We studied the role of α<subscript>1</subscript>-adrenergic receptors (AR) in ischemia-induced neoangiogenesis (NeoA) in vivo in 12-week-old rats in which the right common femoral artery was removed and in vitro in cultured rat endothelial cells (EC). We investigated the effects of 14 days' administration of the α<subscript>1</subscript>-AR antagonist doxazosin (DOXA, 0.06 mg/kg/d, n=16) or saline (CTRL, n=6) by means of peritoneum-implanted osmotic minipumps. Laser Doppler analysis and digital angiography TIMI Frame Count showed an improvement in perfusion of the ischemic hind limb of the DOXA vs CTRL group. Similarly, dyed microsphere perfusion and histologic evaluation confirmed the beneficial effects of DOXA on NeoA. In vitro, we verified by RT-PCR the expression of α<subscript>1</subscript>-AR in EC. DOXA (10<superscript>-7</superscript>M; 24 h) increased EC proliferation in response to fetal bovine serum (FBS, 5%) and enhanced FBS-induced ERK and Rb activation. Our findings support a beneficial role for α<subscript>1</subscript>-AR blockade in ischemia-induced NeoA and on EC proliferation. [ABSTRACT FROM AUTHOR]