Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.
Animal ; Antioxidants/pharmacology ; Antioxidants/metabolism* ; Aorta, Abdominal/ultrastructure ; Aorta, Abdominal/pathology ; Aorta, Thoracic/ultrastructure ; Aorta, Thoracic/pathology ; Butylated Hydroxytoluene/pharmacology ; Butylated Hydroxytoluene/metabolism* ; Cholesterol/metabolism ; Cholesterol, Dietary/metabolism* ; Male ; Microscopy, Electron, Scanning ; P-Selectin/biosynthesis* ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe most intimidatory pathological changes in patients with DM are cardiovascular illnesses, which are the major causes of death in diabetic patients and are far more prevalent than in nondiabetics because of accelerated atherosclerosis. In this study, we tried to clarify the changes in macrovascular endothelial ultrastructure and in the gene expression of endothelial nitric oxide synthase (eNOS)mRNA in diabetic rats.

METHODSThe study was conducted on 52 of 10-week old Sprague Dawley (SD) rats with body weight of (320 +/- 42) g. SD rats were divided into: experimental group treated with a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg), (male, n = 20, diabetes mellitus (DMM)); female, n = 12, diabetes mellitus female (DMF)) and control group (male, n = 10, diabetes mellitus male control (DMMC); female, n = 10, diabetes mellitus female control (DMFC)). Four weeks after treatment, half of the rats were sacrificed; the remainders were sacrificed ten weeks after treatment. One part of the abdominal aortic sample was stored under glutaraldehyde (volume fraction psiB = 2.5%). After the process of chemical fixation, chemical dehydration, drying and conductivity enhancement, all samples were observed and photographed using scanning electron microscopy (Leica-Stereoscan 260, England). The other part of the abdominal aortic sample was treated with liquid nitrogen and the expression of eNOSmRNA was assessed by semi-quantitative RT-PCR.

RESULTSThe aortic lumen of both experimental groups adsorbed much more debris than that of either control group. The endothelial surfaces of diabetic rats were coarse, wrinkled and protuberant like fingers or villi. The vascular endothelial lesions of diabetic male rats were very distinct after 4 weeks, and as obvious as those at 10 weeks. The vascular endothelial lesions of diabetic female rats were not severe at 4 weeks and only became marked after 10 weeks. In both males and females, the abdominal aortic eNOSmRNA content of 4 weeks and 10 weeks diabetic rats was very significantly lower (P < 0.01) than that of controls.

CONCLUSIONSAortic endothelial ultrastructure in DM rats is injured compared with controls. Abnormal changes of aortic endothelia in male DM rats are more obvious than those in females. Expression of abdominal aortic eNOSmRNA content of DM rats is significantly lower than that of controls.

Animals ; Aorta, Abdominal ; enzymology ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; enzymology ; pathology ; Endothelium, Vascular ; ultrastructure ; Female ; Male ; Nitric Oxide Synthase ; genetics ; Nitric Oxide Synthase Type III ; RNA, Messenger ; blood ; Rats ; Rats, Sprague-Dawley ; Sex Factors ; Streptozocin

OBJECTIVETo study the effects of enhanced external counterpulsation (EECP) on the vascular morphology, and endothelial function using experimentally induced hypercholesterolemic pigs.

METHODSThirty five male pigs were randomly divided into three groups: 7 normal control animals, 11 hypercholesterolemic animals, and 17 hypercholesterolemic animals receiving EECP. Serum cholesterol was measured. The coronary arteries and aortas were sampled for histopathologic and ultrastructural examination. The NF-kappaB protein expression of porcine coronary arteries was investigated by immunofluorescence.

RESULTSCompared with the normal controls, serum cholesterol levels were significantly higher in the hypercholesterolemic animals with or without EECP. The plaque/intimal area ratio of the aorta decreased significantly in animals receiving EECP [(3.33 +/- 2.40)%, versus (12.03 +/- 7.12)% in those without EECP, P < 0.05]. Lipid deposition, endothelial damage and proliferation of smooth muscle cells were less severe in animals receiving EECP than those not. Moreover, activation and expression of NF-kappaB also decreased significantly (P < 0.05) in animals receiving EECP.

CONCLUSIONSEECP improves the morphology and function of vascular endothelium, and retards the development and progression of atherosclerosis, likely through the inhibition of NF-kappaB signaling pathway.

Animals ; Aorta, Abdominal ; metabolism ; pathology ; ultrastructure ; Atherosclerosis ; blood ; metabolism ; pathology ; Cholesterol ; blood ; Coronary Vessels ; metabolism ; pathology ; ultrastructure ; Counterpulsation ; methods ; Endothelial Cells ; metabolism ; pathology ; Hypercholesterolemia ; blood ; metabolism ; pathology ; Lipoproteins, LDL ; blood ; Male ; Microscopy, Confocal ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Muscle, Smooth, Vascular ; metabolism ; pathology ; NF-kappa B ; metabolism ; Random Allocation ; Swine