IMPAIRED ADAPTIVE VASCULAR GROWTH IN HYPERCHOLESTEROLEMIC RABBIT

Occlusive arterial disease stimulates compensatory growth of pre-exist ent and new arterial channels which help to maintain organ perfusion. Previous studies characterizing compensatory or collateral vascular gr owth have been performed in normocholesterolemic animals. Because hype rlipidemic states alter vascular regulation, it remains to be demonstr ated that the capacity of the vasculature to undergo compensatory grow th is preserved in the presence of dyslipidemic vascular injury. To as sess effects of hypercholesterolemia on vascular growth, arterial supp ly to the ear of rabbits with (n = 13) or without hypercholesterolemia (n = 14) was surgically restricted. Compensatory growth of residual a rteries and distal microvessels was evaluated using quantitative angio graphic and microanatomic methods. Lumen-expanding hyperplasic arteria l remodelling and distal microvascular proliferation induced by arteri al restriction were assessed by independent techniques including in vi vo microangiography, laser Doppler flowmetry, quantitative histometry, and thymidine incorporation. Compared with controls, hypercholesterol emic rabbits exhibited depressions in all arterial and capillary growt h indexes, Microvascular proliferation in hypercholesterolemic rabbits was less than 20% of control. Results demonstrate for the first time that an atherogenic dyslipidemia may limit compensatory macro- and mic rovascular growth in response to arterial restriction, a phenomenon th at could play an important role in the pathophysiology of atherosclero tic occlusive artery disease. (C) 1998 Elsevier Science Ireland Ltd. A ll rights reserved.