Objective: To explore the mechanism and effect of sodium/hydrogen exchanger (Na(+)-H(+) exchanger, NHE), amiloride, on vessel stenosis.
Methods: Thirty-two adult male New Zealand white rabbits were randomly divided into groups of amiloride intervention (IG, n = 12), balloon injury (BG, n = 10) and sham-operation (SG, n = 10). A 2.5 mm x 20 mm Foley's tube was used to injury left side iliac artery in the IG and BG groups, whereas a same Foley's tube was inserted into the vessel without any injuries in the SG group. Amiloride (5 mg.kg(-1).d(-1)) was intraperitoneally injected 3 days before balloon injuries and the same dosage normal saline was used in the same way in the BG group for 28 days after operation. The rabbits were killed and the iliac arteries were stained with Hematoxylin-Eosin, alpha-actin and Masson's trichrome to observe the morphologic changes in the vessel cava, neointima, media layer, and vascular smooth muscle cells (VSMCs) migration into the neointima and extracellular matrixes (ECMs).
Results: Four weeks after balloon injuries in rabbits, a cave narrow of the iliac artery and neointima were found and the media layer (VSM layer) was proliferated. The quantities of NHE-1 protein from artery smooth muscle in all the groups were 0.21 +/- 0.02, 0.25 +/- 0.04 and 0.11 +/- 0.03 (P < 0.01), respectively. The difference between the BG and SG groups was significant, which indicated that the NHE-1 proteins increased after balloon injury. The quantities of NHE-1 protein from the IG group were lower than those from the BG group. The cave areas were 0.91 mm(2) +/- 0.23 mm(2), 0.68 mm(2) +/- 0.19 mm(2) and 1.08 mm(2) +/- 0.17 mm(2) (P < 0.01), respectively. The intima areas were 0.27 mm(2) +/- 0.15 mm(2), 0.67 mm(2) +/- 0.24 mm(2) and 0.05 mm(2) +/- 0.03 mm(2), respectively (P < 0.01). The ratios of intima to media area were 1.21 +/- 0.24, 1.39 +/- 0.26 and 0.15 +/- 0.08 (P < 0.01), respectively. Amiloride increased vessel cave areas, but decreased intima areas and intima to media ratios in the IG group. In the IG group, alpha-actin positive areas in neointima was higher (16,328.31 microm(2) +/- 6220.27 microm(2)) than those in the SG group (4164.15 microm(2) +/- 1788.37 microm(2)) (P < 0.01). ECMs areas in neointima in the IG group were lower (8910.62 microm(2) +/- 7041.62 microm(2)) than those in the SG group (33,358.76 microm(2) +/- 7290.17 microm(2)) (P < 0.01).
Conclusions: Balloon injuries of iliac artery in rabbits induce VSMCs proliferation, migration, narrowed cave and vessel stenosis. Amiloride, a NHE-1 inhibitor, may relieve this vessel stenosis.