Time course of changes in collateral blood flow and isolated vessel size and gene expression after femoral artery occlusion in rats

1 Biomedical Sciences, College of Veterinary Medicine, 2 Medical Pharmacology and Physiology, College of Medicine, and 3 Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211 Submitted 6 May 2004 ; accepted in final form 7 July 2004 The objectives of this study were to assess the time course of enlargement and gene expression of a collateral vessel that enlarges following occlusion of the femoral artery and to relate these responses to the increases in collateral-dependent blood flow to the calf muscles in vivo. We employed exercise training to stimulate collateral vessel development. Rats were exercise trained or kept sedentary for various times of up to 25 days postbilateral occlusion ( n = 9/time point). Collateral blood flow to the calf muscles, determined with microspheres, increased modestly over the first few days to 40 ml·min –1 ·100 g –1 in sedentary animals; the increase continued over time to 80 ml·min –1 ·100 g –1 in the trained animals. Diameters of the isolated collateral vessels increased progressively over time, whereas an increased vessel compliance observed at low pressures was similar across time. These responses were greater in the trained animals. The time course of upregulation of vascular endotheial growth factor and placental growth factor, and particularly endothelial nitric oxide synthase and fms-like tyrosine kinase 1, mRNAs in the isolated collateral vessel implicates these factors as integral to the arteriogenic process. Collateral vessel enlargement and increased compliance at low pressures contribute to the enlarged circuit available for collateral blood flow. However, modulation of the functioning collateral vessel diameter, by smooth muscle tone, must occur to account for the observed increases in collateral blood flow measured in vivo. peripheral vascular disease; arteriogenesis; exercise training; physiological control of gene expression; angiogenic growth factors Address for reprint requests and other correspondence: R. L. Terjung, Biomedical Sciences, E102 Vet Med Bldg., Univ. of Missouri, Columbia, MO 65211 (E-mail: TerjungR{at}missouri.edu )