The effects of amiloride, a Na+-H+ exchange inhibitor, on iliac artery stenosis after balloon injury in rabbits.
This study was designed to explore the effects of amiloride, a Na+-H+ exchange (NHE) inhibitor, on vessel stenosis by observing the expression of NHE-1 protein in vascular smooth muscle (VSM) after balloon injury and the effects of amiloride on VSM cell proliferation, migration, and excretion of extracellular matrices (ECMs). A total of 32 adult male New Zealand white rabbits were randomly divided into a balloon injury group (BG), an amiloride-treated group (AG), and a sham-operated group (SG). The left iliac artery was injured by inflating a 2.5 mm x 20 mm Foley catheter in BG and AG rabbits; in SG rabbits, the Foley catheter was inserted but not inflated. Amiloride (5 mg x kg(-1) x d(-1)) was injected intraperitoneally in AG and the same volume of distilled water was used in BG 3 days before balloon injury and for 28 days after the injury. The left iliac artery was stained by hematoxylin-eosin, alpha-actin, and Masson's trichrome to observe the vessel cava, neointima, media layer, and ECMs. NHE-1 proteins of the VSM were detected by Western blotting. A narrowing of the arterial cava, neointima formation, and thickened VSM layer were observed 28 days after balloon injury in BG and AG. However, in AG, the vessel cava was not as narrowed as that of BG and the intimal areas were to a lesser extent than in BG. In AG, the alpha-actin-positive areas and the ECM areas in the neointima were increased compared with SG, but to a lesser extent than in BG. The expression of NHE-1 protein in VSM was increased in BG and AG after balloon injury; however, the levels in AG were significantly less than in BG. In conclusion, VSM cell proliferation, migration, and excretion of ECMs contributed to vessel stenosis in the BG and AG rabbits. The expression of NHE-1 protein in VSM increased after balloon injury. Amiloride, an inhibitor of NHE-1, can limit the development of vessel stenosis through inhibition of VSM cell proliferation, migration, and excretion of ECMs.
Fang
Xiao Yi
XY
Department of Pediatrics, First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Lin
Ni Yang
NY
Li
Yu Guang
YG
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D021721:Balloon Occlusion / Q000009:adverse effects*; D002465:Cell Movement / Q000187:drug effects; D003251:Constriction, Pathologic; D004232:Diuretics / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D007083:Iliac Artery / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects
D004232:Diuretics; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D000584:Amiloride