p 16 基因对人肝癌细胞的生长抑制作用的初步研究

目的探讨抑癌基因p16对肝癌细胞生长的抑制作用。方法将p16 cDNA亚克隆至pcDNA3.1真核表达载体上,并经脂质体介导转染至人肝癌细胞株SMMC-7721。用MTT法和Western blot分析转染细胞的生长情况。结果成功构建重组表达质粒pcDNA3.1-p16,转染pcDNA3.1-p16的SMMC-7721细胞生长速度受到明显抑制;经Western blot证实,转染后有外源p16蛋白的表达,且伴随Bax上调,Bcl-2和cIAP2的下调。结论重组pcDNA3.1-p16质粒能在人肝癌细胞SMMC-7721内表达,且能抑制SMMC-7721的生长,其机理与诱导肿瘤细胞凋亡相关。     

周期蛋白D1正反义表达质粒的构建鉴定及其对哮喘大鼠气道平滑肌增殖的影响

观察哮喘大鼠气道平滑肌周期蛋白D1的表达，并构建大鼠周期蛋白D1 (CyclinD1)正反义表达质粒，转染支气管哮喘大鼠气道平滑肌细胞(ASMC)，探讨CyclinD1在哮喘大鼠ASMC增殖过程中的影响。大鼠雾化吸入卵清蛋白建立哮喘模型，免疫荧光检测CyclinD1的表达。以气道平滑肌条总RNA为模板，通过RT-PCR获取大鼠CyclinD1全长cDNA，插入到真核表达载体pcDNA3.1(+)上，构建CyclinD1正义表达质粒(pcDNA3.1-CyclinD1)和反义表达质粒(pcDNA3.1-asCyclinD1)。用脂质体介导的基因转染方法，将正反义重组体和空质粒(vector)分别转染哮喘大鼠和正常大鼠ASMC，用Western blotting方法鉴定CyclinD1基因的表达。采用流式细胞术、四甲基偶氮唑盐(MTT)法、增殖细胞核抗原(PCNA)染色等方法观察构建质粒对哮喘大鼠ASMC增殖的影响。结果表明：(1)与对照组相比，哮喘组CyclinD1表达显著增高；(2)酶切鉴定和测序分析证实，试验成功构建了CyclinD1正反义表达质粒。与转染pcDNA3.1-CyclinD1组和vector组相比，转染pcDNA3.1-asCyclinD1组大鼠ASMC中CyclinD1表达水平下降(P<0.01)；(3)与vector组S+G₂M期比例、吸收度(A)值、PCNA阳性表达率相比，转染pcDNA3.1-CyclinD1组增殖指标均明显增加(P<0.01)。转染pcDNA3.1-asCyclinD1组增殖指标均明显下降(P<0.01)。正常组大鼠转染质粒后各组间变化趋势与哮喘组一致。pcDNA3.1-CyclinD1可促进哮喘大鼠ASMC增殖，pcDNA3.1-asCyclinD1可抑制哮喘大鼠ASMC增殖，提示CyclinD1在哮喘ASMC增殖的信号转导中具有重要作用。     

凝血栓蛋白-1Ⅰ型重复序列反义核酸在血管内皮细胞中的作用研究

目的探讨TSP-1Ⅰ型重复序列反义RNA对人脐静脉血管内皮细胞(human umbilical vein endothelial cells,HU-VECs)生长活性、增殖活性影响。方法构建TSP-1Ⅰ型重复序列反义RNA真核表达载体(pcDNA3.1-/anti-TSP-1-Ⅰ),经双酶切、测序及Western blot鉴定后,转染HUVECs。采用MTT法检测转染后HUVECs活性改变,流式细胞仪检测转染后HUVECs周期变化,透射电镜观察转染后HUVECs形态学改变。结果构建的pcDNA3.1-/anti-TSP-1-Ⅰ经鉴定后转染HUVECs,MTT法检测所得HUVECs OD值较未转染组、pcDNA3.1-空载体转染组升高(均P<0.01);流式细胞仪检测结果显示:pcDNA3.1-/anti-TSP-1-Ⅰ转染HUVECs后S+G2(%)较未转染组、pcDNA3.1-空载体转染组S+G2(%)延长(均P<0.01);透射电镜结果显示:pcDNA3.1-/anti-TSP-1-Ⅰ转染后HUVECs核仁相对增多。结论TSP-1反义RNA能够促进HUVECs增殖和生长。     

CYP1A1对人血管内皮细胞内钙的影响

目的探讨CYP1A1对人血管内皮细胞HVEC304细胞内钙的影响,探索CYP1A1的内源性作用。方法构建CYP1A1的红色荧光表达载体,转染人血管内皮细胞,激光共聚焦检测细胞内的钙离子浓度。结果CYP1A1表达载体在人血管内皮细胞中成功表达,定位于细胞质。过表达CYP1A1的HVEC304细胞(HVEC304-CYP1A1)中游离钙的浓度明显低于未转染的HVEC304细胞(P<0.01)。随着veratridine浓度的上升,HVEC304-CYP1A1细胞中游离钙的水平逐渐上升。结论过表达CYP1A1人血管内皮细胞中,钙离子基础水平明显降低,veratridine可以剂量依赖性地逆转这一作用。     

Construction and identification of eukaryotic expression plasmids containing SLPI gene

目的 构建并鉴定含分泌型白细胞蛋白酶抑制蛋白(SLPI)基因的重组真核表达质粒.方法 以HeLa细胞的总RNA为模板,用RT-PCR方法扩增出SLPI基因cDNA,将产物克隆进真核载体pcDNA3.1(+)内,构建含SLPI基因的重组真核表达质粒.将pcDNA-SLPI重组质粒和空载体peDNA分别转染HeLa细胞,Western blot检测SLPI蛋白表达.结果 核酸序列分析及双酶切鉴定SLPI已成功插入pcDNA3.1(+)载体中,转染pcDNA-SLPI的HeLa细胞中检测到高表达的SLPI蛋白.结论 成功构建了含SLPI基因的重组真核表达质粒.     

SLPI基因真核表达质粒的构建和鉴定

目的构建并鉴定含分泌型白细胞蛋白酶抑制蛋白(SLPI)基因的重组真核表达质粒。方法以HeLa细胞的总RNA为模板,用RT-PCR方法扩增出SLPI基因cDNA,将产物克隆进真核载体pcDNA3.1(+)内,构建含SLPI基因的重组真核表达质粒。将pcDNA-SLPI重组质粒和空载体pcDNA分别转染HeLa细胞,Western blot检测SLPI蛋白表达。结果核酸序列分析及双酶切鉴定SLPI已成功插入pcDNA3.1(+)载体中,转染pcDNA-SLPI的HeLa细胞中检测到高表达的SLPI蛋白。结论成功构建了含SLPI基因的重组真核表达质粒。     

参麦注射液对大鼠心脏细胞色素P450酶的调节作用

目的研究参麦注射液及各单药注射液对大鼠心脏P450酶mRNA表达和花生四烯酸代谢的影响。方法 SD大鼠连续腹腔注射参麦注射液及各单药注射液14 d后取心脏,采用实时荧光定量PCR(RT-q PCR)方法,检测各处理组药物对大鼠心脏P450亚酶CYP1A1、CYP1B1、CYP2B1、CYP2C11、CYP2E1、CYP2J3、CYP4A1、CYP4A3、CYP4F1、CYP4F4、CYP4F5、CYP4F6、ANP、BNP、EPHX2mRNA表达的影响。结果对各处理组的心脏P450酶mRNA表达水平检测显示:与空白组比较,除CYP2B1、CYP4A3和CYP4F6参麦注射液对其他CYP各亚型mRNA的表达均表现了上调的作用,红参注射液组对CYP2E1、CYP4A3、CYP4F1和EHPX2mRNA表达有上调作用,麦冬注射液对ANP、BNP和EHPX2mRNA的表达上调作用明显,同时能明显下调CYP2B1和CYP2C11的表达。结论虽然参麦注射液对CYP2B1的作用没有统计学意义,但总体呈现出诱导的趋势,而麦冬注射液对CYP2B1呈现明显的抑制作用,提示红参注射液可能对CYP2B1的诱导作用更大。参麦注射液、红参注射液与麦冬注射液均对CYP2E1、CYP4F1和EHPX2有诱导作用,提示参麦注射液对CYP2E1、CYP4F1和EHPX2的诱导作用可能由复方中的红参和麦冬共同贡献。参麦注射液和麦冬注射液对ANP和BNP均具有诱导的作用,提示在对ANP和BNP的作用中麦冬比红参的作用更强。同时参麦注射液对心血管疾病疗效明确,可能与其对CYP2J3、ANP和BNP等调节作用较强相关。     

S100A11过表达对人胰腺癌细胞PANC-1增殖的影响

目的探讨钙囊素(S100A11)过表达对人胰腺癌细胞PANC-1增殖的影响。方法构建S100A11过表达载体质粒pcDNA3.1-S100A11,并转染人胰腺癌细胞PANC-1细胞。Western blot检测转染效果;CCK-8检测转染后PANC-1细胞增殖活力;流式细胞术检测PANC-1细胞的凋亡和细胞周期的变化。结果 S100A11蛋白表达量与pcDNA3.1-S100A11的转染量成正相关。过表达S100A11基因可明显提高PANC-1细胞增殖速度,降低凋亡细胞比例,并使PANC-1细胞S期细胞比例增加,G1期细胞减少(P<0.05)。结论S100A11过表达能调控PANC-1细胞周期,并促进PANC-1细胞的增殖。     

大鼠FasL基因重组慢病毒载体介导大鼠肾细胞体外转染

目的 探讨慢病毒载体对大鼠肾细胞体外转染的可行性.方法 三质粒系统共转染包装细胞293-T,合成重组慢病毒载体,P24gag EIISA对其定量测定.流式细胞术测定SD大鼠肾细胞Fas、FasL的表达.Western blot、RT-PCR检测转染后目的 基因的表达.结果 定量测定目的 基因载体、空白载体浓度分别为11.6 ng/ml、13.8 ng/ml,Western blot、RT-PCR分别检测到目的 基因的表达.结论 慢病毒载体体外成功转染SD大鼠肾细胞,并表达目的 基因.     

人乳腺癌转移抑制基因真核表达载体的构建及鉴定

目的 构建乳腺癌转移抑制基因(BRMS 1)的真核表达载体pcDNA3.1(-)B/myc-BRMS1,为进一步研究恶性肿瘤的转移机制及基因治疗提供物质基础.方法 常规方法培养人乳腺癌细胞株MCF-7,Trizol法提取细胞株总RNA;设计一对特异性引物,经过逆转录反应获得BRMS1 cDNA的CDS序列,连接到质粒pcDNA3.1/myc-His(-)B上,构建BRMS 1的真核表达载体pcDNA3.1(-)B/myc-BRMS1,行基因测序鉴定正确后转染人胚肾细胞HEK-293,行Western blot验证其是否表达.结果 重组质粒pcDNA3.1(-)B/myc-BRMS 1经双酶切及基因测序分析,验证了克隆的人BRMS 1基因cDNA序列与GenBank[AF159141]公布的人BRMS 1基因的cDNA序列吻合,重组体pcDNA3.1(-)B/myc-BRMS 1中插入的目的 基因BRMS 1是正向、单倍插入.结论 成功构建了BRMS 1真核表达载体pcDNA3.1(-)B/myc-BRMS 1,为深入研究BRMS 1基因功能和BRMS 1基因治疗奠定了物质基础.     

Recombinant adeno-associated virus-mediated delivery of antisense angiotensin II receptor 1 gene attenuates hypertension development

Aim：The renin-angiotensin system plays a crucial role in the development and establishment of hypertension, and the pharmacological blockade of the system results in a reduction in blood pressure. In the present study, we investigated whether the effects of a novel, double-stranded, recombinant adeno-associated virus vector （rAAV）-mediated antisense angiotensin Ⅱ receptor 1 （AT1R） gene efficiently prevents the development of hypertension induced by a high-salt diet in adult, male Sprague-Dawley （SD） rats. Methods：A rAAV was prepared with a cassette containing a cytomegalovirus promoter and partial cDNA （660 base pairs） for the AT1R inserted in the antisense direction （rAAV-AT1-AS）. A single tail vein injection of the rAAV-AT1-AS or rAAV-GFP （green fluorescent protein, a reporter gene） was performed in adult, male SD rats. Two weeks after injection, the animals were fed a diet containing 8% NaCl, and the systolic blood pressure was measured weekly using the tail-cuff method for 12 weeks. Results： The high-salt diet induced a significant rise in systolic blood pressure in the rAAV-GFP-treated animals; however, the rAAV-AT1-AS treatment attenuated the rise in blood pressure （142.7±4.5 mmHg vs 117±3.8 mmHg, P〈0.01）, and the hypotensive effect was maintained until the experiments ended at 12 weeks. In the rAAV-GFP-treated animals AT1 was overexpressed in various tissues, especially in the aorta and kidney at mRNA levels; in contrast, rAAV-AT1-AS treatment markedly attenuated AT1 expression. Furthermore, rAAV-AT1-AS treatment prevented target organ damages from hypertension, including cardiac dysfunction and renal injury compared to the rAAV-GFP group. Conclusion：These results suggest that rAAVmediated anti-AT1 delivery attenuates the development of hypertension and protects against renal injury and cardiac remodeling.     

ROLE OF THE SYMPATHETIC NERVOUS SYSTEM IN THE ONSET OF HYPERTENSION IN THE RAT: THE EFFECT OF 6-OH-DOPAMINE

1. The effect of chemical sympathectomy with 6-OH-dopamine (6-OHDA) on the onset of adrenocorticotrophin (ACTH)-induced hypertension was examined in Sprague-Dawley rats (n = 23). 2. 6-OHDA injection produced a fall in systolic blood pressure (SBP) from 100 +/- 5 mmHg control to 74 +/- 4 mmHg post-6-OHDA Treatment Day 1 (P less than 0.001), but did not alter food or water intake, urine volume or electrolyte excretion. 3. Compared with sham injection, ACTH-treated rats showed an increase in blood pressure (sham: 98 +/- 7 mmHg; ACTH: 123 +/- 9 mmHg on Treatment Day 10; P less than 0.01), loss of bodyweight, and increases in water intake and urine volume. 4. The magnitude of the blood pressure rise on ACTH was greater in 6-OHDA-treated rats than in intact control rats. Metabolic changes were similar. 5. Chemical sympathectomy with 6-OHDA did not delay or block the onset of ACTH hypertension in the rat.     

Blood pressure during a combination of ketanserin and hydrochlorothiazide

The antihypertensive effectiveness of a combination of ketanserin 20 mg plus hydrochlorothiazide 25 mg has been evaluated in 20 patients with arterial hypertension of mild to moderate degree in the age group over 50 years (age range 50-78 years). After a wash-out period of at least two weeks, patients were given a single oral dose of ketanserin 20 mg or thiazide 25 mg in a randomized order at two-day intervals and blood pressure, heart rate and cardiac workload (systolic blood pressure x heart rate) were measured during the following 24 h by an automatic recorder. Thereafter patients were given the combination of the two drugs for six weeks and 24 h blood pressure was assessed after the first dose and at the end of the treatment. A significant fall in systolic and diastolic blood pressure was rapidly induced by ketanserin from 2 to 8 h after dosing; thiazide on the other hand did not induce any change in these parameters (169 +/- 15/95 +/- 6 mmHg (22.5 +/- 2.0/12.7 +/- 0.8 kPa) at baseline versus 153 +/- 17/89 +/- 7 mmHg (20.4 +/- 2.3/11.9 +/- 0.9 kPa) at 2 h and 157 +/- 19/87 +/- 8 mmHg (20.9 +/- 2.5/11.6 +/- 1.1 kPa) at 8 h on ketanserin; 166 +/- 15/93 +/- 6 mmHg (22.1 +/- 2.0/12.4 +/- 0.8 kPa) at baseline versus 160 +/- 12/89 +/- 6 mmHg (21.3 +/- 1.6/11.9 +/- 0.8 kPa) at 2 h and 157 +/- 15/89 +/- 5 mmHg (20.9 +/- 2.0/11.9 +/- 0.7 kPa) at 8 h on thiazide).(ABSTRACT TRUNCATED AT 250 WORDS)     

ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats

We hypothesize that endothelin-A receptor stimulation contributes to the elevated blood pressure and superoxide production in endothelin-B receptor-deficient rats on a high salt diet. Experiments were conducted on homozygous endothelin-B-deficient (sl/sl) and wild-type rats (wt) fed a high salt diet (8% NaCl) for 3 weeks. Separate groups were given normal drinking water or water containing the endothelin-A receptor antagonist, ABT-627 (5 mg/kg per day; n = 8-9 in all groups). On a normal salt diet, (sl/sl) rats had a significantly elevated systolic blood pressure compared with wt (138 +/- 3 vs 117 +/- 4 mmHg, respectively; P < 0.05). High salt diet caused a significant increase in systolic blood pressure in (sl/sl) rats compared with wt (158 +/- 2 vs 138 +/- 3 mmHg, respectively; P < 0.05). Endothelin-A receptor blockade decreased systolic blood pressure in (sl/sl) rats on high salt (125 +/- 5 mmHg; P < 0.05 vs without antagonist) without affecting the systolic blood pressure in wt (119 +/- 4 mmHg). Aortic superoxide production (lucigenin chemiluminescence) and plasma 8-isoprostane were elevated in sl/sl rats and were significantly reduced by endothelin-A receptor blockade in sl/sl, but not in wt rats. These findings suggest that endothelin-1, through the endothelin-A receptor, contributes to salt-induced hypertension and vascular superoxide production in endothelin-B-deficient rats.     

Prevention by blockade of angiotensin subtype1-receptors of the development of genetic hypertension but not its heritability.

1. We determined whether early inhibition of angiotensin II subtype1 (AT1) receptors by the newly synthesized nonpeptidic antagonist, A-81988, can attenuate the development of hypertension in spontaneously hypertensive rats (SHR) and if the altered blood pressure phenotype can be passed on to the subsequent generation, not exposed to the antagonist. 2. Pairs of SHR were mated while drinking tap water or A-81988 in tap water, and the progeny was maintained on the parental regimen until 14 weeks of age. At this stage, A-81988-treated rats showed lower systolic blood pressure and body weight values (136 +/- 5 versus 185 +/- 4 mmHg and 247 +/- 4 versus 283 +/- 4 g in controls, P < 0.01); while heart rate was similar. In addition, mean blood pressure was reduced (101 +/- 7 versus 170 +/- 7 mmHg in controls, P < 0.01), and the pressor responses to intravenous or intracerebroventricular angiotensin II were inhibited by 27 and 59%, respectively. Heart/body weight ratio was smaller in A-81988-treated rats (3.2 +/- 0.1 versus 3.8 +/- 0.1 in controls, P < 0.01). 3. The antihypertensive and antihypertrophic effect of A-81988 persisted in rats removed from therapy for 7 weeks (systolic blood pressure: 173 +/- 4 versus 220 +/- 4 mmHg, heart/body weight ratio: 3.4 +/- 0.1 versus 4.1 +/- 0.1 in controls at 21 weeks of age, P < 0.01 for both comparisons), whereas the cardiovascular hypertensive phenotype was fully expressed in the subsequent generation that was maintained without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

DIETARY Ng-NITR0-l-ARGININE INDUCES SUSTAINED HYPERTENSION IN NORMOTENSIVE WISTAR-KYOTO RATS

1. Prolonged oral administration of NG-nitro-L-arginine (L-NNA) for a period of 5 weeks in 8 week old male normotensive Wistar-Kyoto (WKY) rats (n = 10), induced hypertension in all animals. Hypertension was characterized by a sharp initial increase in both systolic blood pressure (SBP) and mean blood pressure (MBP) until the third day (from 126 +/- 3 mmHg to 160 +/- 6 mmHg and from 95 +/- 3 mmHg to 133 +/- 6 mmHg, respectively). This was followed by a gradual and steady increase until the fourth week (163 +/- 4, 171 +/- 3 and 189 +/- 8 mmHg for SBP in weeks 1, 2 and 4, respectively; and 135 +/- 4, 143 +/- 3 and 157 +/- 5 mmHg for MBP in weeks 1, 2 and 4, respectively). 2. Intravenously L-arginine.HCl (500 mg/kg) administered on the last day of the 5th week abolished the effect of dietary L-NNA on the arterial blood pressure. 3. Dietary L-NNA-induced hypertension in WKY rats is easily obtainable and free of any surgical operation, and can be utilized as a new experimental model to further understand the importance of endothelium-dependent relaxing factor/nitric oxide in blood pressure regulation and to clarify the pathological significance in intact animals where endothelium-dependent relaxing factor/nitric oxide is functionally involved.     

Vasopressin and the pathogenesis of chronic renal failure.

1. Partial (5/6) renal ablation was performed in Long Evans rats treated with vehicle or a vasopressin V1-receptor antagonist, in control Long Evans rats, and in homozygous Brattleboro rats which lack endogenous vasopressin. 2. In control and vasopressin-blocked Long Evans rats, 3 weeks following partial renal ablation, systolic blood pressure was 215 +/- 5 and 199 +/- 9 mmHg and, urinary protein excretion was 54 +/- 4 and 50 +/- 3 mg day-1, respectively. 3. The pressor response to exogenous vasopressin was significantly (P less than 0.05) reduced in rats treated with the V1-receptor antagonist (ED50 mmHg 5.0 +/- 1.6 vs. 0.09 +/- 0.01 micrograms kg-1). 4. In control Long Evans and in Brattleboro rats, 3 weeks following renal ablation, systolic blood pressure was 204 +/- 10 and 191 +/- 7 mmHg, and urinary protein excretion was 97 +/- 27 and 71 +/- 5 mg day-1, respectively. 5. Histological examination of the remaining kidney tissue demonstrated significant glomerular hyalinization following renal ablation but no differences between any of the groups. 6. The data indicate that neither vasopressin nor the urinary concentrating mechanism is likely to be involved in the hypertension and proteinuria associated with partial renal ablation.     

INHIBITION OF NO SYNTHESIS HAS AN ADDITIVE EFFECT ON HYPERTENSION INDUCED BY ACTH IN CONSCIOUS RATS

1. The haemodynamic and metabolic effects of oral intake of approximately 30 mg/kg per day N-nitro-L-arginine (NOLA) were examined in sham and adrenocorticotrophin (ACTH, 0.5 mg/kg per day) treated conscious Sprague-Dawley rats (n = 33). 2. NOLA administration produced an increase in systolic blood pressure of 24 +/- 6 mmHg (P < 0.001), but did not alter food or water intake, urine volume or electrolyte excretion in rats not treated with ACTH. 3. Compared with sham injection, ACTH-treated rats demonstrated an increase in systolic blood pressure (water + sham, 3 +/- 1 mmHg; water + ACTH, 16 +/- 3 mmHg; P < 0.001), loss of bodyweight, and increases in water intake and urine volume. 4. The magnitude of the blood pressure rise in ACTH-treated rats was greater in those receiving NOLA than in those drinking water only (water + ACTH, 16 +/- 3 mmHg; NOLA + ACTH, 37 +/- 3 mmHg; P < 0.05). Metabolic changes were similar. 5. Inhibition of nitric oxide is unlikely to be a major determinant of ACTH-induced hypertension in the rat, since NOLA increased blood pressure whether or not ACTH was administered, indicating an additive effect of ACTH and NOLA administration.     

Enhanced blood pressure sensitivity to DOCA-salt treatment in endothelin ET(B) receptor-deficient rats

The role of endothelin ET(B) receptor-mediated action in the development and maintenance of deoxycorticosterone acetate (DOCA)-salt-induced hypertension was evaluated using the spotting-lethal (sl) rat which carries a naturally occurring deletion in the ET(B) receptor gene. Homozygous (sl/sl) rats treated with DOCA-salt for 1 week exhibited an earlier onset of hypertension than heterozygous (sl/+) and wild-type (+/+) rats (systolic blood pressure, SBP; 156.7+/-3.4 versus 128.8+/-5.3 and 132.9+/-3.7 mmHg, respectively). Four weeks after the start of DOCA-salt treatment, homozygous rats developed marked hypertension, with a SBP of 206. 0+/-4.5 mmHg, compared with 184.8+/-10.7 mmHg in heterozygous and 164.3+/-4.8 mmHg in wild-type rats. Cardiovascular hypertrophy and renal dysfunction observed after 4-weeks treatment with DOCA-salt were more severe in homozygous rats, compared to wild-type and heterozygous animals. These evidences support strongly the view that ET(B) receptor-mediated actions are a protective factor in the pathogenesis of DOCA-salt-induced hypertension.     

Increased arterial distensibility induced by the angiotensin-converting enzyme inhibitor, lisinopril, in normotensive rats.

1. We investigated possible structural correlates of the beneficial effect of chronic angiotensin-converting enzyme inhibition (ACEI) with lisinopril on the aortic distensibility of normotensive rats. 2. Experiments were performed in young (4-month old), normotensive, Wistar rats which received lisinopril in their drinking water (0.9 or 9 mg kg-1 day-1) for 9 months. 3. Following ACEI treatment, rats were pithed and aortic pulse wave velocity was measured during the progressive rise in mean arterial blood pressure produced by i.v. infusion of the alpha 1-adrenoceptor agonist, phenylephrine. The slope of the regression line relating aortic pulse wave velocity to mean arterial blood pressure was taken as an index of aortic distensibility. Following this, the aorta was fixed in situ at a normotensive pressure level and histomorphometry was performed. We also measured the calcium content of the aortic wall by atomic absorption. 4. The lower dose of lisinopril failed to lower systolic arterial blood pressure (unanaesthetized rat) or mean arterial blood pressure (pithed rat). Chronic ACEI with the higher dose of lisinopril lowered both systolic arterial blood pressure (104 +/- 6 mmHg, controls 133 +/- 4 mmHg, unanaesthetized), and mean arterial blood pressure (27 +/- 1 mmHg, controls 34 +/- 2 mmHg, pithed). 5. Although the lower dose of lisinopril did not lower blood pressure, it did improve aortic distensibility as revealed by a fall in the slope relating aortic pulse wave velocity (Y) to mean arterial blood pressure (X). Values were 5.7 +/- 0.7, 3.8 +/- 0.6 and 2.7 +/- 0.3 in controls, and in low and high ACEI groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)