替米沙坦治疗慢性充血性心力衰竭疗效观察

目的 探讨慢性充血性心力衰竭时替米沙坦对病人肾素活性、血管紧张素Ⅱ水平和血流动力学的影响。方法 120例老年慢性充血性心力衰竭病人随机分为替米沙坦组和依那普利组各60例,疗程12周。测定肾素活性、血管紧张素Ⅱ水平,用超声心动图测定治疗前、治疗12周后心功能、血流动力学变化。结果 两组治疗12周后．心功能改善至Ⅰ～Ⅱ级,多项血流动力学指标如左心室射血分数、短轴缩短率、每搏量、心输出量、心脏指数、左心室舒张末期内径等均获改善,与治疗前比较差异有统计学意义（P＜0.05）,治疗前、后两组比较差异均无统计学意义（P＞0.05）。治疗后,替米沙坦组血管紧张素Ⅱ水平改变无统计学意义（P＞0.05）;但依那普利组血管紧张素Ⅱ水平降低。结论与依那普利比较,替米沙坦治疗老年慢性充血性心力衰竭疗效相似,改善临床症状和多项血流动力学指标,并且有较好的耐受性。     

Imdomethacin Reduces the Antihypertensive Action of Enalapril

We evaluated the influence of indomethacin on the pharmacological actions of Enalapril in 9 uncomplicated essential hypertensives. While on chronic treatment with Enalapril, these patients randomly received indomethacin (50 mg bid) or a corresponding placebo for 1 week and the opposite treatment after a 2 week interval. Indomethacin, which decreased serum thromboxane B2 and urinary 6-keto prostaglandin-F1 alpha, reduced the plasma renin activity (PRA) increased by Enalapril. Indomethacin did not modify serum ACE, whose activity had been reduced by the ACE inhibitor. Mean blood pressure (MBP) values, which were significantly and to a similar extent reduced by Enalapril at the beginning of the cross-over, after placebo addition and at the end of the two week interval, were significantly increased by indomethacin, despite being still significantly lower than baseline values. These data show that systemic and renal prostaglandin (PG) synthesis inhibition induced by indomethacin can blunt the antihypertensive effect of chronic Enalapril treatment in patients with essential hypertension.     

The Clinical Application of Converting Enzyme Inhibitors

Chronic blockade of the renin angiotensin system became possible when orally active inhibitors of angiotensin converting enzyme, the enzyme which catalyzes the transformation of angiotensin I into angiotensin II, were synthetized. Two compounds, captopril and enalapril, have been investigated in clinical studies. The decrease of the pressor response to exogenous angiotensin I and of the circulating levels of angiotensin II following administration of these inhibitors has been demonstrated to be directly related to the degree of suppression of plasma angiotensin converting enzyme activity. These inhibitors have been shown to normalize blood pressure alone in some hypertensive patients whereas in many others, satisfactory blood pressure control can be achieved only after the addition of a diuretic. Captopril and enalapril also markedly improve cardiac function of patients with chronic congestive heart failure. Chronic blockade of the renin angiotensin system has therefore provided an interesting new approach to the treatment of clinical hypertension and heart failure.     

Role of Angiotensin II in the Hypertension Induced by Renal Artery Stenosis

Identical degrees of renal artery stenosis were induced in 5 dogs on two separate occasions; once during continuous inhibition of angiotensin I converting enzyme with enalapril, and once with the dogs untreated. Arterial pressure rose about 25 mm Hg during 3 days of stenosis in untreated dogs, due to increased total peripheral resistance. When the dogs were treated with enalapril, blood pressure had risen 14.5 ± 3.4 mm Hg 24 hours after stenosis due to a 35% increase in cardiac output while total peripheral resistance fell by 16%. By the third day, blood pressure had returned to pre-stenosis levels, cardiac output was close to normal and total peripheral resistance had increased. The stenosis on the renal artery increased the resistance to blood flow of the kidneys in both untreated and enalapril treated dogs. This increase in kidney resistance in the untreated dogs accounted for about 30% of the change in total peripheral resistance. In the enalapril treated dogs, the increased kidney resistance helped offset the vasodilatation in the rest of the vasculature. These results suggest that angiotensin II mediated vasoconstriction of nonrenal vascular beds was responsible for about ? of the hypertension following renal artery stenosis, and the resistance of the stenosis responsible for about ?.     

依那普利干预肾素-血管紧张素系统对老龄鼠心房颤动诱发率的影响

目的研究依那普利对老龄鼠心房颤动(简称房颤)诱发率的影响。方法雄性老龄Wistar大鼠(12月龄)随机分为对照组(n=12)和实验组(n=13),对照组常规饲养,实验组加喂依那普利。3个月后,描记体表Ⅰ导联心电图,测量心率和P波时限。在体研究右房有效不应期(ERP)、房间传导时间(IACT)和心房对刺激的反应。用放免法测量血浆和心房组织血管紧张素Ⅱ(AngⅡ)浓度。取心房组织制作切片,测量纤维组织占总区域的百分比。结果实验组较对照组P波时限和IACT缩短(P均<0.01)。实验组房颤诱发率较对照组低[30.8%(4/13)vs75%(9/12),P=0.027]。实验组左、右房组织匀浆AngⅡ浓度较对照组降低(P均<0.01)。实验组大鼠左房和右房纤维化程度均较对照组明显减轻(P均<0.01)。结论老龄鼠长期应用依那普利后房颤诱发率降低,这可能是由于依那普利降低了心房纤维化程度,改善了心房传导。     

坎地沙坦治疗轻、中度原发性高血压164例临床疗效观察

目的评价坎地沙坦酯治疗轻中度高血压的疗效及安全性。方法入选164例轻中度高血压患者,经2周导入期后随机分为试验组和对照组各82例,按双盲、平行临床药理试验方法分别给予坎地沙坦酯8mg和依那普利10mg治疗。治疗4周后如不能有效控制血压,则将用药剂量加倍并维持到第8周末。检测患者治疗前后不同时间的血压、心率,以及血、尿常规,肝、肾功能,并记录服药期间可能发生的不良事件。结果试验组降压有效率为90．24％,对照组降压有效率为82．93％,治疗后2周末收缩压（SBP）和舒张压（DBP）均已明显降低。此后血压继续下降,与治疗前相比,用药8周末试验组和对照组SBP分别下降37．1和34．1mmHg,DBP分别下降18．4和14．01／mmHg。试验组中有1例患者服药期间出现头痛,1例患者感轻微胸痛和腹胀。两组患者血、尿常规,肝、肾功能均正常。结论坎地沙坦酯治疗轻中度高血压降压效果良好,服用安全。     

依那普利对老年高血压病病人左室舒张功能改善的临床观察

应用平衡法放射性核素心室造影，观察了依那普利（悦宁啶）对老年高血压病患者左室舒张功能的影响。结果表明：血压治疗后较治疗前明显降低，其中收缩压治疗后（１８．５±１．８ｋＰａ）较治疗前（２２．５±２．７ｋＰａ）明显下降（Ｐ＜０．０１），舒张压治疗后（１０．６±１．１ｋＰａ）较治疗前（１３．７±１．４ｋＰａ）明显下降（Ｐ＜０．０１），左室舒张功能得到不同程度改善。平均充盈率（ＭＦＲ）治疗后（１．５００４±０．３５２３）较治疗前（１．３９１１±０．４０８５）明显提高（Ｐ＜０．０１）；１／３充盈分数（１／３ＦＦ）治疗后（０．３４４５±０．１３０４）较治疗前（０．２７７９±０．１１５）明显提高（Ｐ＜０．０１）。提示依那普利在有效地降低血压的同时，亦能确切地改善左室舒张功能。     

依那普利对糖尿病大鼠肾脏保护作用的实验研究

目的 研究依那普利对糖尿病大鼠肾脏的保护作用。方法 应用依那普利对糖尿病大鼠进行了１０周治疗,观察了其对糖尿病大鼠肾脏的保护作用。结果 对照组糖尿病大鼠肾小球滤过度,肾血流量,滤过分数及尿白蛋白均较正常对照组明显升高,肾小球基底膜不规则增厚,突触融合。依那普利治疗后糖尿病大鼠ＧＦＲ,ＲＰＦ,ＦＦ及ＵＡ均较糖尿病对照组明显降低,病理学异常不明显。     

依那普利对NIDDM并微白蛋白尿患者的作用

在无明显临床肾病征象的177例NIDDM中检出微白蛋白尿患者18例(10.2％)。采用单盲随机交叉实验设计,对其中14例用血管紧张素转换酶(ACE)抑制剂依那普利(Enalapril,E)和钙通道阻滞剂尼群地平(Nitrendipine,N)治疗。结果表明E不但是NIDDM合并高血压患者的有效降压药之一,且对正常血压或高血压NIDDM合并微白蛋白尿者,具有不依赖于其降压效应而减少尿蛋白的作用     

依那普利和硝苯地平控释片对早期糖尿病肾病合并高血压的疗效比较

目的　观察依那普利和硝苯地平控释片对早期糖尿病肾病合并高血压患者血压及尿白蛋白排泄率 (UAER)的影响。方法　随机将 44例病人分为 2组 :依那普利组 (10 mg,2次 /d,2 2例 ) ;硝苯地平控释片组 (30 mg,1次 /d,2 2例 )。疗程 6个月 ,观察治疗前后血压及 UAER的变化。结果　两组治疗后均能明显降低血压 (P <0 .0 1)及 UAER,由 90 .2和 86 .0分别降至 6 7.4和70 .8,下降 2 9.1%和 2 3.5 % ,P值均 <0 .0 1,但两组比较差异无显著性 (P>0 .0 5 )。两组治疗后U AER下降幅度与收缩压、舒张压下降幅度之间比较无显著相关性 (P值均 >0 .0 5 )。结论　依那普利和硝苯地平控释片均能有效降低血压 ,减少尿蛋白的排泄 ,保护肾脏功能