胆囊切除术对家兔Oddi括约肌运动功能的影响

目的探讨胆囊切除术对家兔Oddi括约肌运动功能变化的影响。方法将16只成年家兔随机分成正常对照组、胆囊切除术组,每组8只。手术4周后进行Oddi括约肌压力及肌电的同时测定。结果压力测定:胆囊切除术组胆总管压力降低,Oddi括约肌基础压、收缩波幅升高(P<0.01);肌电测定:肌电活动由原来的锋电位变为肌电簇,波幅升高,持续时间延长(P<0.01),收缩频率未见明显变化。结论胆囊切除术后家兔Oddi括约肌功能有明显改变;Oddi括约肌蠕动增强以加快胆汁的排泄。     

豚鼠急性胆囊炎对Oddi括约肌的影响

目的：观察豚鼠急性胆囊炎时Oddi括约肌形态和功能变化，探讨胆源性急性胰腺炎的发病机制。方法：英国短毛种豚鼠20只，随机分为两组，对照组（A组），开腹后浆膜接触电极测Oddi括约肌肌电活动，用4/25 powerLab压力转换系统测量胆管内压力；急性胆囊炎组（B组）开腹后胆囊内注射大肠杆菌和胆石混悬液诱发急性胆囊炎。饲养10 d后再次开腹测肌电活动和胆管及Oddi括约肌压力，并观察其病理组织学变化。结果：B组Oddi括约肌的肌电振幅、肌电簇持续时间、基础压、峰压和收缩频率明显高于A组（P＜0.01）；与A组比，B组光镜下Oddi括约肌内炎性细胞浸润，平滑肌组织排列紊乱，有较多的胶原纤维和结缔组织。结论：急性胆囊炎时，豚鼠Oddi括约肌肌电振幅、肌电簇持续时间、基础压、峰压和收缩频率明显异常，病理组织学出现炎性细胞浸润和平滑肌组织排列紊乱。     

同步检测胆囊及Oddi氏括约肌电活动和胆管压力的兔模型

目的 建立同步检测胆囊及Oddi括约肌肌电活动及胆囊、胆总管压力的动物模型.方法 对6只家兔用7F静脉深穿管分别经肝穿刺进入胆囊腔及经十二指肠腔插入胆总管.将铂金电极缝在胆囊底部浆膜上.以多通道生理仪记录家兔的胆囊及Oddi括约肌肌电信号和胆囊、胆总管压力.结果 Oddi氏括约肌肌电的峰电位＞0.05 mV,最大电位为0.26 mV,频率为0～2次/分;而慢波电位≤0.05 mV,频率为8⒍11次/分.胆囊内压力最大为15 cm H2O(6.83～15.00 cm H2O),胆总管最大压力为22 cm H2O(11～22 cm H2O).胆囊肌电活动的波形缺乏规律性.结论 兔可以作为同步检测胆囊及Oddi氏括约肌肌电活动和胆囊、胆总管压力的模型.     

胆道口括约肌运动功能与豚鼠胆固醇结石形成关系的研究

目的研究胆道口(Oddi)括约肌运动功能在豚鼠胆囊胆固醇结石形成过程中的作用。 方法34只成年雄性Hartley豚鼠随机分为胆固醇结石组(24只)和对照组(10只),其中胆固醇结石组(按被处死的时间,分为4个亚组,各6只)给予致石饮食,3、6、9、12周后对两组行胆道口括约肌测压并检测肌电活动。 结果胆固醇结石组3、6、9、12周的发生率分别为0、16.7%、16.7%、83.3%。肌电活动的频率在3周组和6周组减小(均P < 0.05),肌电活动幅度在9周组和12周组明显降低[从(146.44 ± 81.09) μV分别降至(68.18 ± 49.58) μV和(40.60 ±45.03) μV, P <0.05]。胆道口括约肌收缩频率在6周组和9周组明显减小(P < 0.05)。胆道口括约肌基础压及胆总管压在12周组明显升高[从(25.19 ± 7.77) mmHg至(52.38 ± 12.84) mmHg,(22.35 ± 7.60) mmHg至(50.11 ± 12.59) mmHg,均P < 0.01]。 结论致胆固醇结石饮食能诱发胆道口括约肌功能紊乱,其张力增加、活动性下降。胆道口括约肌运动功能紊乱是胆色素结石形成的一个重要因素。     

研究Oddi括约肌肌电活动的实验动物模型的建立

目的探讨将家兔用于研究Oddi括约肌肌电活动的实验动物模型的可行性和稳定性。方法对不同条件下的家兔采用双极金属钩状电极采集其肌电活动信号，经放大、滤波及计算机处理后记录其大小及波形。结果不同条件下的家兔Oddi括约肌的肌电活动在波形、频率、强度等方面均有明显的不同，具有明显的规律性。重复实验可得到相同的结论。结论家兔是研究Oddi括约肌肌电活动较为理想的动物，具有价格低廉、来源广泛、信号稳定等优点。使用双极金属钩状电极可以稳定地采集到在体的Oddi括约肌肌电活动信号，这为今后广泛、深入地研究Oddi括约肌肌电活动搭建了一个技术平台。     

Oddi括约肌肌电活动实验模型的建立

目的建立研究Oddi括约肌肌电活动的动物模型和实验方法。方法将双极金属钩状电极通过浆膜层置入Oddi括约肌，记录不同条件干预下家兔的Oddi括约肌肌电活动信号，调整电生理实验参数并经放大、滤波及计算机处理后，对其大小、波形、幅度进行分析。结果不同条件干预下的家兔Oddi括约肌的肌电活动在波形、频率、幅度等方面均有明显的不同，具有明显的规律性。重复实验可得到相似的结果。结论使用双极金属钩状电极配以合理的电生理实验参数调整可以稳定地采集到在体的家兔Oddi括约肌肌电活动信号。这为今后广泛、深入地研究Oddi括约肌肌电活动搭建了一个技术平台。     

Oddi括约肌功能异常在兔肝内胆管结石形成中的作用

目的 探讨Oddi括约肌(Sphincter of Oddi,SO)功能异常与肝内胆管结石形成的关系.方法 建立家兔肝内胆管结石模型;;成年家兔(n=64)随机分为对照组(n=16)和实验组(n=48),实验组再分为2周,4周,8周组(每组n=16),比较各组胆汁性状及成石率,测定s0肌电,透射电镜观察SO超微结构.结果 8周组家兔成形结石形成率(68.75%,11/16)显著高于4周组(12.50%,2/16)和2周组(0.00%,0/16);肌电测定提示:与对照组比较,实验组SO肌电峰值逐渐减低,频率逐渐减慢.电镜超微结构表现:对照组及2周组SO无变性;实验组4周和8周组SO肌纤维溶解、胶原增多,微丝融合、增粗,致密斑减少、排列紊乱,线粒体、内质网肿胀,核周间隙增宽、核偏移及核固缩,胞质中髓样包涵体形成.其变性程度8周组＞4周组.结论 SO运动功能异常与肝内胆管结石形成存在密切联系,两者互为因果.SO肌纤维变性是其运动功能异常的病理基础.     

黏膜接触电极在家兔Oddi括约肌肌电测量中的应用价值

目的 探讨适合Oddi括约肌（sphincter of Oddi,SO）肌电测量的新方法.方法 两组各15只家兔分别用黏膜接触电极（contact electrode on mucosa,CEM）和浆膜钩状电极（chorion claw electrode,CCE）测量SO肌电活动;另外6只家兔同时使用两种电极同步测量.结果 CEM测量SO肌电成功率高,创伤小,而且记录到的家兔SO肌电波形和CCE相比没有明显的差别.结论 CEM是一种很有价值的测量SO肌电活动的新方法,将来可能用于人体SO功能的研究,为人体内镜诊断SO功能提供了一个新方法.     

一氧化氮与胆囊收缩素对犬Oddi括约肌的作用

目的 探讨一氧化氮和胆囊收缩素(CCK)在犬Oddi括约肌运动调节中的作用.方法 测定正常状态及注射CCK、硝普钠、一氧化氮合酶(NOS)抑制剂N-硝基-L-精氨酸甲酯(L-NAME)时,犬Oddi括约肌的基础压、时相收缩频率、时相收缩幅度;免疫组织化学染色法检测犬Oddi括约肌上NOS阳性神经元的表达情况.计量资料的比较采用t检验.结果 注射0、20 ng/kg CCK后,犬Oddi括约肌基础压、时相收缩频率、时相收缩幅度分别为(27±10)mm Hg(1 mm Hg=0.133 kPa)、(10±3)次/min、(32±8)mm Hg和(61±14)mm Hg、(64±21)次/min、(44±15)mm Hg;注射100 ng/kg CCK后产生最大抑制作用和最大兴奋作用时,犬Oddi括约肌基础压、时相收缩频率、时相收缩幅度分别为(77 +31)mm Hg、(69±18)次/min、(79±14)mm Hg和(140±21)mm Hg、(129±25)次/min、( 173±63)mm Hg.胆总管滴注硝普钠后,犬Oddi括约肌基础压、时相收缩幅度均下降(t =3.706,5.183,P＜0.05).而注射L-NAME后,犬Oddi括约肌基础压、时相收缩幅度均升高(t=5.859,3.588,P＜0.05).结论 20 ng/kg生理剂量的CCK可舒张犬Oddi括约肌,大剂量CCK可兴奋犬Oddi括约肌;一氧化氮对犬Oddi括约肌发挥舒张效应,此效应可能在CCK的抑制通路中发挥重要作用.     

Oddi括约肌肌电活动的基本方式

目的 探讨家兔Oddi括约肌(sphincter of Oddi,SO)肌电活动的基本方式及其生物学意义.方法 32只家兔随机分为4组.第1组(n=8)为空腹组;第2组(n=8)为进食组,空腹18 h后经胃造瘘管注入50 ml牛奶;第3组(n=8)为Nardi test激发实验组,静脉注射1 mg吗啡和1 mg新斯的明;第4组(n=8)为神经阻断组,记录空腹家兔肌电活动30 min后静脉给予山莨菪硷1 mg;两对钩状双极金属电极通过浆膜层分别置于SO及十二指肠,使用RM6240多道生理信号采集处理系统同时记录每一组家兔SO及十二指肠肌电活动,连续记录SO肌电活动120～150 min.结果 空腹状态下家兔SO肌电表现为规律的、单发性的SPSO;进食后家兔SO肌电活动表现为规律的、间断的MASO;Nardi test激发实验后SO肌电活动表现为数个长时间、不间断的SPSO组成的肌电串;阻断神经节后胆碱能神经元后SO肌电活动规律随即消失,120 min后SPSO逐渐恢复到空腹状态.结论 家兔SO肌电活动存在4种基本形式,即空腹状态下SO保持一定基础紧张性的基本张力波;进食后SO开始蠕动将胆汁排入十二指肠的蠕动波;Nardi test激发实验后SO处于持续关闭状态的痉挛波;阻断胆碱能神经元后SO处于松弛状态的舒张波.提示SO并非仅仅存在"非开即闭"两种形式.这对今后有关SO基础研究和临床治疗均具有理论指导意义.     

Iron deficiency transiently suppresses biliary neuronal nitric oxide synthase

BACKGROUND: Iron deficiency results in altered gallbladder and sphincter of Oddi (SO) motility and cholesterol crystal formation. In addition, gallbladder neuronal nitric oxide synthase (nNOS) has been shown to be markedly reduced after 8 weeks on an iron-deficient diet. However, the effects of prolonged iron deficiency on gallbladder and SO nNOS as well as crystal formation have not been determined. Therefore, we tested the hypothesis that iron deficiency would downregulate both gallbladder and SO nNOS expression and that nNOS downregulation and cholesterol crystal formation would progress over time. MATERIALS AND METHODS: Thirty-eight adult female prairie dogs were fed either an ironsupplemented (Fe+) (200 ppm) or an iron-deficient (Fe-) (8 ppm) diet for 8 weeks (Fe+ n = 9, Fe- n = 10) or 16 weeks (Fe+ n = 9, Fe- n = 10). Blood hemoglobin (HbG) was measured; gallbladder cholesterol crystals were counted; and cholesterol saturation indices (CSI) were calculated. Gallbladder and SO nNOS levels were measured by Western blot. RESULTS: The Fe+ prairie dogs had significantly higher HbG than the Fe- animals (16.9 +/- 0.6 g/dl vs 15.2 +/- 0.5 g/dl, respectively, P < 0.05) after 8 weeks. This difference was even greater after 16 weeks (16.1 +/- 0.4 g/dl vs 14.0 +/- 0.5 g/dl, P < 0.01). At 8 weeks, more cholesterol crystals per 10 HPF were observed in the Fe- animals (0.4 +/- 0.3 vs 1.6 +/- 0.4 per 10 HPF, P < 0.05). This difference was even greater after 16 weeks (0.0 +/- 0.0 vs 52.6 +/- 25.3 per 10 HPF, P < 0.01). No difference in the CSI was observed in the four groups. Iron deficiency decreased the nNOS/beta-actin protein levels in the gallbladder and SO at 8 weeks (57.0 +/- 29.6 vs 7.4 +/- 2.6, gallbladder, P < 0.05) (98.4 +/- 39.7 vs 29.9 +/- 11.0, SO, P = 0.09), but these levels returned to baseline at 16 weeks. CONCLUSIONS: We conclude that iron deficiency acutely suppresses gallbladder and SO nNOS, and that compensatory mechanisms return nNOS to baseline levels while cholesterol crystal formation increases over time.     

Renal injury of diet-induced hypercholesterolemia in rats

Abnormalities in lipid metabolism frequently accompany renal disease and may be important in the pathogenesis of progressive renal injury. In the present study, the effects of a high cholesterol diet on renal histology, cortical lipids, and glomerular hemodynamic function were examined in normal rats with and without reduced renal mass. Cholesterol feeding for 19 weeks increased serum cholesterol from 66 +/- 10 mg/dl to 256 +/- 93 mg/dl in two-kidney rats, and from 73 +/- 15 mg/dl to 407 +/- 274 mg/dl in nephrectomy rats (P less than 0.01). Both sham-operated and unilateral nephrectomy rats fed a high cholesterol diet had a greater amount of glomerulosclerosis and tubulointerstitial damage than rats fed standard chow. Cortical cholesteryl esters were increased by the cholesterol diet, and correlated with the amount of glomerulosclerosis (r = 0.90, P less than 0.01) and tubulointerstitial injury (r = 0.64, P less than 0.05). Cholesterol feeding and nephrectomy both caused alterations in tissue essential fatty acids, and a panel of specific monoclonal antibodies indicated that renal injury and cortical lipid alterations were associated with an increase in glomerular macrophages. Finally, micropuncture experiments carried out in a separate group of rats fed high cholesterol for 8 to 10 weeks demonstrated increases in glomerular capillary pressure. These results suggest that additional investigations may ultimately determine how cholesterol deposition, altered fatty acid metabolism, macrophages, and increased glomerular pressure might combine to cause chronic progressive renal injury.     

金粉蕨素对动脉粥样硬化兔血脂的影响

目的探讨金粉蕨素对实验性动脉粥样硬化兔血脂的影响。方法 21只健康大耳白兔,随机分为3组,分别给予正常饲料、高脂饲料、高脂饲料加金粉蕨素,观察8周,测定兔血浆中TC、TG、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量,并且观察三组实验动物的主动脉病理学形态改变。结果对动脉粥样硬化兔给予金粉蕨素可以明显降低兔血浆中TG、TC、LDL-C含量,差异具有统计学意义（P〈0.05）,而且金粉蕨素可有效减小高脂饲料引起的兔动脉粥样硬化斑块面积。结论金粉蕨素具有较强的抗动脉粥样硬化作用,给予金粉蕨素治疗8周,胆固醇含量明显下降。深入探讨金粉蕨素的作用机制将为动脉粥样硬化的治疗及新药开发提供新的思路。     

Renal vascular function in hypercholesterolemia is preserved by chronic antioxidant supplementation

Hypercholesterolemia impairs systemic vascular reactivity in response to endothelium-dependent vasodilators, which may be mediated partly through increased formation of lipid peroxides. However, it is unclear whether these pathophysiological mechanisms play a role in renal vascular impairment in experimental hypercholesterolemia. Hence, pigs were studied after a 3-mo normal (n = 7) or high cholesterol (HC) (n = 7) diet, HC diet supplemented daily with antioxidant vitamins E (100 IU/kg) and C (1000 mg; HC+vitamins, n = 5), or normal diet supplemented with vitamins (N+vitamins, n = 5). Renal blood flow was measured with electron-beam computed tomography before and during infusion of acetylcholine (Ach). Endothelial function, endothelial and inducible nitric oxide synthase (NOS), and nitrotyrosine immunoreactivity were studied in renal arteries ex vivo. Despite similar cholesterol levels, LDL oxidizability (lag time, malondialdehyde, and relative electrophoretic mobility) was increased in pigs that were fed the HC diet but was significantly decreased in pigs that were fed the HC+vitamins diet. Renal blood flow response to Ach was blunted in pigs that were fed the HC diet but was preserved in pigs that were fed the HC+vitamins diet. Maximal relaxation to Ach was attenuated in pigs that were fed the HC diet compared with those that were fed the normal diet (51.5 +/- 6.4% versus 97.0 +/- 2.9%; P < 0.01) but was preserved in pigs that were fed the HC+vitamins diet (103.1 +/- 3.0%; P = 0.39) and N+vitamins diet (87.7 +/- 3.0%; P = 0.1), as were relaxation responses to calcium ionophore A23187. Vascular smooth-muscle relaxation to diethylamine was enhanced in endothelium-denuded HC vessel but was restored in pigs that were on the HC+vitamins regimen. In HC, immuno-reactivity of endothelial NOS was decreased, that of inducible NOS was increased, and both were preserved in pigs that were fed the HC+vitamins and N+vitamins diets, whereas nitrotyrosine was not detected. The present study demonstrates that antioxidant intervention in experimental HC reduces LDL oxidizability and preserves renal vascular responses to endothelium-dependent vasodilators. Therefore, this beneficial effect potentially can protect the kidney from hypercholesterolemia-induced damage.     

高含量胆固醇诱导动脉粥样硬化性阴茎勃起功能障碍动物模型的建立及机制探讨

目的 :采用高含量胆固醇建立动脉粥样硬化性阴茎勃起功能障碍 (ED)动物模型并探讨其诱发ED机制。　方法 :30只雄性新西兰大白兔 ,随机分为 2组 :普通饲料 (ND)组 1 0只 ,喂以普通饲料 ;高胆固醇组 2 0只 ,喂以含 1 .5 %胆固醇的饲料。处理 1 2周后观测血脂水平、升主动脉斑块和阴茎勃起情况 ,测定阴部内动脉内膜 /中膜厚度比值 ,以及RT PCR法检测阴部内动脉中血管细胞粘附分子 (VCAM 1 )mRNA表达水平。　结果 :实验过程中共有 5只新西兰大白兔死亡 ,高胆固醇组 3只 ,对照组 2只。喂饲含 1 .5 %胆固醇饲料的新西兰大白兔 1 2周后均出现高脂血症 ,其中 9只发生典型的动脉粥样硬化 (为ATH组 ) ,动脉粥样硬化诱导成功率为 5 2 .9%。ATH组和HCH组 (喂饲高胆固醇但未发生典型动脉粥样硬化者 )TC、TG、AI均显著高于ND组 (P <0 .0 1 )。ATH和HCH组新西兰大白兔阴茎勃起率及阴茎勃起次数均明显降低 ,其中尤以ATH组降低更显著 (P <0 .0 1 )。ATH组阴部内动脉内膜 /中膜厚度比值和VCAM 1mRNA表达水平显著高于HCH和ND组 (P <0 .0 1 )。　结论 :采用高含量胆固醇喂饲新西兰大白兔建立ED动物模型较为简便、可行可靠。高胆固醇血症可能通过VCAM 1损害动脉内皮细胞功能 ,造成动脉内膜增厚、管腔狭窄等所致的阴茎供血不足     

Involvement of endothelial nitric oxide synthase in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbit

The present study was designed to evaluate whether functional impairment and/or protein expression of constitutive nitric oxide synthase (cNOS; endothelial NOS [eNOS] and neuronal NOS[nNOS]) was involved in impairment of endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. New Zealand White rabbits were randomly divided into control and experimental groups. The control group (n=20) received a regular diet, while the two experimental groups (n=20 for each) were fed a 2% cholesterol diet for 4 and 8 weeks, respectively. We conducted isometric tension studies with endothelium-dependent and endothelium-independent vasodilators with or without preincubation with L-arginine and nonadrenergic, noncholinergic (NANC)-selective electrical field stimulation on isolated strips of corpus cavernosum. Expression of cNOS (eNOS and nNOS) protein was assessed by Western blot analysis. cNOS activities in both cytosolic and particulate fractions were measured by determining the conversion of L-[U-14C] arginine to L-[U-14C] citrulline. Blood levels of cholesterol were significantly higher (P < 0.01) in the experimental groups than in the control group. The relaxation responses to endothelium-dependent agents (acetylcholine and adenosine 5'-diphosphate [ADP]) were significantly reduced (P < 0.05) in both experimental groups, regardless of their incubation with L-arginine, compared with the control group. However, no differences were found among the three groups in the relaxation response to endothelium-independent agents (papaverine and nitroprusside) and to NANC-selective electrical field stimulation. There was no difference in immunoreactive nNOS from cytosolic and particulate fractions between the cavernous tissues of the control and experimental groups. nNOS protein levels in the particulate fractions were markedly lower than in the cytosolic fractions. The particulate cNOS activity was significantly decreased (P < 0.05) in the experimental groups compared with the control group, while the cytosolic cNOS activity in the experimental groups was not different from that found in the control group. Therefore, it is concluded that functional impairment of eNOS, rather than of nNOS, may lead to impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli in hypercholesterolemic rabbits.     

Vitamin E prevents steroid-induced osteonecrosis in rabbits

Background and purpose Prevention of osteonecrosis after corticosteroid administration would be important. We examined the potential of vitamin E (α-tocopherol) to reduce the incidence of corticosteroid-induced osteonecrosis in an animal model.

Methods Japanese white rabbits were divided into 2 groups; the control group was fed a normal diet and the experimental group was fed α-tocopherol-supplemented diet in which α-tocopherol (600 mg/kg diet) was added to the normal diet. To induce osteonecrosis, high-dose methylprednisolone acetate (MPSL) (20 mg/kg body weight) was injected once into the right gluteus medius muscle of all rabbits. 4 weeks after the injection of MPSL, the presence or absence of osteonecrosis of bilateral femurs was examined histopathologically. The tocopherol/cholesterol ratios were calculated. The plasma levels of thiobarbituric acid-reactive substances (TBARS) were measured.

Results Alpha-tocopherol-supplemented diet reduced the incidence of osteonecrosis, which developed in 14 of 20 rabbits in the control group and 5 of 21 rabbits in the experimental group (p = 0.004). The tocopherol/cholesterol ratio was higher in the experimental group than in the control group after the α-tocopherol administration. The plasma TBARS level was lower in the experimental group than in the control group at 4 weeks after the MPSL administration.

Interpretation Our findings may offer a new approach for the prevention of corticosteroid-induced osteonecrosis.     

Regional patterns of bone loss and altered bone remodeling in response to calcium deprivation in laboratory rabbits

Summary This study explores the effects of a calcium-deficient diet on patterns of bone remodeling, and examines regional differences in the amount of bone lost. Skeletally mature female rabbits (n=6) were fed a calcium-deficient diet (0.10% Ca²⁺ and 0.50% P) for 14 weeks. A separate group of rabbits (n=4) were fed a maintenance diet (1.2% Ca²⁺ and 0.45% P). Bone mineral content, serum calcium, and serum phosphorus were measured each week during the experimental period. Following sacrifice, the L₃ vetebra, femoral head, proximal tibial metaphysis, and tibial midshaft were analyzed histomorphometrically. Rabbits had 20% less vertebral bone after only 14 weeks of a calcium-deficient diet. As in human postmenopausal osteoporosis, bone loss in calcium-deficient rabbits occurs in the trabecular bone of the lumbar spine before that in the trabecular bone of the lower extremity. Calcium-deficient diets alone do not lead to increased osteoid volume or thickness. Because bone loss is relatively rapid and because the pattern of loss is similar in some respects to that found in humans, adult rabbits may provide an attractive model of calcium deficiency osteoporosis in a skeletally mature mammal in which remodeling is predominant over modeling.     

Intracavernosal injections of vascular endothelial growth factor protects endothelial dependent corpora cavernosal smooth muscle relaxation in the hypercholesterolemic rabbit: a preliminary study.

Atherosclerosis is a major risk factor for erectile dysfunction, and loss of endothelium-dependent vasodilation appears early in the development of this disorder. Nitric oxide (NO) appears to be the principle mediator of erectile function and is generated in part by the sinusoidal endothelium. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and an endothelial cell-specific mitogen and the actions of VEGF are coupled to NO. In this preliminary study, we investigated whether VEGF could be used to protect endothelial dependent cavernosal relaxation from the atherosclerotic injury induced by a hypercholesterolemic diet.Two groups of New Zealand white adult male rabbits received a 1% cholesterol diet for four weeks, and two groups consumed normal rabbit chow. Half of the rabbits consuming the 1% cholesterol diet received weekly penile injections of 0.3 mg VEGF (n=8), and half injections of normal saline (n=8). Rabbits fed normal chow followed a similar protocol, half received weekly penile injections of 0.3 mg VEGF (n=6) and half were given weekly penile injections of normal saline (n=6). Isometric tension studies (with norepinephrine, acetylcholine, sodium nitroprusside and histamine) were performed on isolated strips of corpora cavernosa. The degree of corporal smooth muscle relaxation in response to ACH and SNP administration was recorded and compared.Significant elevation in serum total cholesterol levels occurred in rabbits receiving 4 weeks of the 1% cholesterol diet (727+/-75.6 mg/dl vs 38.7+/-5.53 mg/dl) P<0.01. There were no significant differences in cavernosal contraction in any group, while cavernosal smooth muscle from rabbits on normal chow retained the ability to relax in response to ACH and SNP in tissue bath. The hypercholesterolemic rabbits receiving VEGF had a significantly higher maximal per-cent relaxation to ACH (111+/-28.9) compared to the hypercholesterolemic rabbits that received NS (77+/-23.1, P<0.001). This difference in percent maximal relaxation to SNP was also present for hypercholesterolemic/VEGF rabbits (129.4+/-24) versus the hypercholesterolemic/NS rabbits (115.0+/-18, P=0.033).In conclusion, intracavernosal injections of VEGF appear to protect corporal endothelium from hypercholesterolemia induced injury, thus preserving endothelial dependent corporal smooth muscle relaxation in hypercholesterolemic rabbit.