title: [Protective effect of Na(+)-H+ exchanger inhibitor cariporide on the injury of vascular endothelial function induced by hypercholesterolemia].
abstract: OBJECTIVE
  To explore possible effects of cariporide, a new Na(+)-H+ exchanger (NHE-1) inhibitor, against injuries of vascular endothelial function induced by hypercholestrolemia.
  
  
  METHODS
  Twenty-two healthy New Zealand rabbits were randomly divided into 3 groups: Six were fed with normal diet as the control; eight were fed with high cholesterol plus high fat diet (HCHF) as the injured control group; and the other eight were fed with HCHF plus cariporide orally (0.1 mg/kg.d-1) as the treated group. The animals were weighed and their blood was drawn from the central ear artery to analyze plasma cholesterol at the pre-experiment and in the 10th week of postexperiment. The animals were killed in the 10th week and the aortic artery was isolated to analyze vascular endothelial function.
  
  
  RESULTS
  1. The HCHF diet significantly attenuated endothelium-dependent relaxation (EDR) of rabbit aortic rings to acetylcholine (ACh), but cariporide significantly protected against HCHF diet-injured EDR of rabbit aortic rings. The dose-response curves elicited by ACh from HCHF diet rabbits were more significantly shifted to the right than those from HCHF diet plus HOE 642-treated rabbits. 2. The HCHF diet and cariporide did not significantly influence the endothelium-independent relaxation of the rabbit artery elicited by sodium nitroprusside (SNP). 3. There was no significant difference in the levels of total cholesterol and LDL-C between the HCHF diet and the HCHF diet plus cariporide rabbits.
  
  
  CONCLUSIONS
  The Na(+)-H+ exchanger (NHE-1) inhibitor can protect against injuries of vascular endothelial function induced by hypercholesterolemia. The activized Na(+)-H+ exchangers of cellular membranes may be involved in injuries of vascular endothelial function induced by hypercholesterolemia.
authors.affiliation: Department of Pharmacology, Xiangya School of Medicine, Central South University, Changsha 410008, China.
authors.forename: Jiang-hua
authors.initials: JH
authors.lastname: Tu
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D006146:Guanidines / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D017942:Nitric Acid / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011817:Rabbits; D011897:Random Allocation; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D017942:Nitric Acid; C093373:cariporide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II