Long-term reduction of intimal hyperplasia by the selective alpha-1 adrenergic antagonist doxazosin.
Studies have shown that alpha 1-adrenergic blockade reduces intimal hyperplasia in the rabbit aorta. In this study a selective alpha 1-adrenergic antagonist, doxazosin, has been used to examine whether this effect is persistent and dose dependent. Forty-eight New Zealand White rabbits underwent endothelial denudation of the abdominal aorta using a Fogarty balloon catheter. Test rabbits were given low-dose (2 mg) or high-dose (8 mg) doxazosin daily and all animals killed at either 1 or 12 weeks after the procedure. The aortas were harvested after fixation in situ with 4 per cent glutaraldehyde and neointimal hyperplasia was measured, using an x-y digitizer, as the percentage reduction in luminal cross-sectional area. At 1 week after surgery, rabbits receiving the low dose had a median area reduction of 7.7 per cent and those receiving the high dose a reduction of 8.2 per cent; both had significantly less intimal hyperplasia than control rabbits, which had a median area reduction of 14.8 per cent (P < 0.01). However, at 12 weeks, when compared with the 32.6 per cent reduction in the control group, only those rabbits receiving high-dose doxazosin had significantly less intimal hyperplasia, with a reduction of 5.5 per cent (P < 0.001). It is concluded that selective alpha 1-adrenergic blockade significantly reduces neointimal hyperplasia, that this effect is dose dependent, and that it persists for at least 3 months.
Vashisht
R
R
Department of Surgery, Charing Cross and Westminster Medical School, London, UK.
Sian
M
M
Franks
P J
PJ
O'Malley
M K
MK
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D011817:Rabbits; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology*
D017292:Doxazosin