title: Angiotensin converting enzyme inhibition enhances collateral artery remodeling in rats with femoral artery occlusion.
abstract: Evidence from experimental animal studies indicate that ACE inhibition expands collateral blood flow both in ischemic hearts and peripheral limbs. The present study evaluates whether ACE inhibitor induces collateral blood flow expansion and change of angiogenic gene expression profile in collateral arteries during remodeling. Male Sprague-Dawley rats, weighing 350 g were treated with vehicle (control) or quinapril (ACE inhibitor) at either low dose (3.0 mg/kg) or high dose (18 mg/kg) for 1, 3, 7, 14 days (gene expression) or 16 days (blood flow). All rats received bilateral occlusions of the femoral arteries. Collateral blood flow to the hind limb was assessed by 85Sr and 141Ce-labeled microspheres during treadmill running at 15 and 25 m/min speeds. Quinapril reduced plasma ACE activity by 58% and 88% for the low-dose and high-dose groups, respectively (P < 0.001). High-dose quinapril reduced exercising blood pressure (P < 0.05) and increased hind limb conductance. Collateral blood flows to calf muscles were 51 +/- 3.7, 73 +/- 5.0, and 68 +/- 1.9 mL/min per 100 g in control and quinapril low- and high-dose groups, respectively, during high-speed running (P < 0.001). Real-time RT-PCR revealed that ACE inhibition shifted gene expression to a proangiogenic phenotype in the newly developed collateral arteries. Our findings indicate that ACE inhibition could increase collateral-dependent blood flow and collateral vessel remodeling by promoting proangiogenic gene expression in newly developed collateral arteries. Our results support the potential utility of ACE inhibitor as a therapeutic agent in treating peripheral occlusive arterial disease.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65211-5120, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Barry M
authors.initials: BM
authors.lastname: Prior
authors.forename: H T
authors.initials: HT
authors.lastname: Yang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D000077583:Quinapril; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril