Enalapril in the treatment of hypertension with renal artery stenosis

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in angiotensin I; this probably reflects the fall in renin substrate that occurs with converting enzyme inhibition. Enalapril alone caused reduction in exchangeable sodium, with distinct increases in serum potassium, creatinine, and urea. Enalapril was well tolerated and controlled hypertension effectively long term; only two of the 20 patients required concomitant diuretic treatment.     

Captopril in renovascular hypertension: long-term use in predicting surgical outcome

The angiotensin converting-enzyme inhibitor captopril was used as long-term preoperative treatment in a series of hypertensive patients with unilateral renal arterial disease. There were immediate and sustained falls in plasma angiotensin II and aldosterone concentrations, with converse increases in circulating renin and angiotensin I. In patients with sodium and potassium deficiency and secondary aldosterone excess before treatment captopril corrected the sodium and potassium deficits; in these cases the initial hypotensive response was profound but the later effect was less pronounced. When sodium and potassium state was initially normal it remained unchanged during captopril treatment, while the full hypotensive effect took up to three weeks to be attained. The immediate, but not long-term, falls in arterial pressure with captopril were proportional to the immediate decrements of plasma angiotensin II. Nevertheless, while the immediate blood-pressure reduction with captopril variously overestimated and underestimated the eventual surgical response, the absolute blood-pressure values during long-term captopril related well with those after operation. Pretreatment plasma renin and angiotensin II concentrations, while closely predicting the immediate captopril response, are fallible guides to surgical prognosis. In contrast, long-term treatment with converting-enzyme inhibitors may provide an accurate indication of surgical outcome.     

Predictive value of angiotensin II antagonists in renovascular hypertension

An angiotensin II antagonist, sarcosine-1, threonine-8 angiotensin II ( [Sar1, Thr8] A II), was infused preoperatively in 14 patients with renal artery stenosis. Postoperative graft patency was documented by renal flow scan in 13 patients. One of these required antihypertensive therapy immediately after surgery, while the other 12 had a significant BP reduction in the first postoperative week (141 +/- 3.7 to 110 +/- 1.6 mm Hg). With longer follow-up, six patients remained normotensive (group 1), while the other six had "residual hypertension" (group 2). There was no significant difference between the two groups as regards age, preoperative BP level, plasma renin activity, blood volume, or response to [Sar1, Thr8] A II. In contrast, clinical signs were most helpful in predicting response to surgery. "Cured" patients had shorter duration of hypertension (less than one year) than patients with residual hypertension, and less impairment of renal excretory function; three patients in group 2 but none in group 1 had a history of malignant hypertension. The decision to operate remains a multifactorial evaluation and cannot be based on results of any single test alone.     

Impaired arginine-vasopressin secretion associated with hypoangiotensinemia in hypernatremic dehydrated elderly patients

Nine elderly patients, some with preceding dementia, presented with adipsia, progressive dehydration, impaired consciousness, and hypernatremia following common acute infections without gastrointestinal disturbance. Studies before rehydration revealed inappropriately low plasma arginine-vasopressin (AVP) levels for plasma osmolality, insufficiently concentrated urine, absolutely or relatively low plasma angiotensin II (A-II) concentrations (compared with plasma renin activity and plasma angiotensin I concentrations), and low serum angiotensin I-converting enzyme activities. The plasma AVP concentrations were positively correlated with the plasma A-II concentrations (r = .677) but not with plasma osmolality. The plasma AVP level was raised by an intravenous infusion of A-II in one patient. These findings suggest the following sequence of events: impaired A-II production caused impairment of thirst perception, renal-concentrating capacity, and AVP secretion and contributed to development of hypernatremic dehydration in these elderly patients.     

冠心病患者血浆内皮素和循环激素变化的临床观察

本文对９０例冠心病患者，３０例正常人应用放免法测定了血浆内皮素、肾素、血管紧张素Ⅱ、心钠素和皮质醇的含量。结果显示在稳定、不稳定型心绞痛和心肌梗塞患者血浆ＥＴ、ＡＴⅡ水平均较正常组显著增高，不稳定型心绞痛和心肌梗塞组较稳定型心绞痛组增高更为明显，血浆ＡＮＦ水平在不稳定型心绞痛和心肌梗塞组中有明显增高。     

Protective effect of the angiotensin-converting enzyme inhibitor perindopril on diabetic glomerulopathy in streptozotocin-induced diabetic rats.

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Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity.

Seven patients with essential hypertension and seven patients with hypertension associated with renal artery stenosis received captopril (SQ 14225), an inhibitor of angiotensin I converting enzyme. There was a significant reduction in mean blood pressure, from 176/113 +/- 4/3 mm Hg during the control period to 140/90 +/- 5/3 mm Hg during captopril administration. Five patients received captopril alone and nine patients needed hydrochlorothiazide in addition to control their blood pressure. Captopril produced a significant increase in peripheral plasma renin activity. When measured 12 hours after the administration of captopril the angiotensin I converting enzyme activity was found to be similar to that during the control period even though the blood pressure was at or near normal. These findings indicate that although captopril is an effective antihypertensive agent, its action does not depend only on inhibition of plasma angiotensin I converting enzyme activity.     

非酒精性脂肪肝患者肾素－血管紧张素系统变化及缬沙坦胶囊对其影响的研究

目的：：探讨非酒精性脂肪肝( nonalcoholic fatty liver disease, NAFLD)患者血浆中的肾素－血管紧张素系统( renin－angiotensin system, RAS)在疾病变化过程中的关系,并进行相关分析。方法：随机收集于我院就诊的经过临床相关血液指标、肝脏彩超等临床诊断确诊的88例 NAFLD 患者做为NAFLD组,同时选取90例健康体检者为对照组做为对比参照, NAFLD 组采用口服缬沙坦胶囊进行干预治疗,在治疗干预前后分别检测患者血浆中丙氨酸氨基转移酶( ALT)、谷氨酰基转移酶( GGT)、甘油三酯( TG)、总胆固醇( TCHO)、空腹血糖( GLU)、肾素活性( Plasma renin activity, PRA)、血管紧张素Ⅰ( AngiotensinⅠ, AngⅠ)、血管紧张素Ⅱ( Angiotensin Ⅱ, Ang Ⅱ),将所得数据进行比较并分析其与NAFLD的关系。结果：NAFLD组在未进行干预治疗前,患者血浆中RAS ( P RA、AngⅠ、Ang Ⅱ)、ALT、GGT、TG、TCHO、GLU与对照组相比较均呈升高,差异具有统计学意义( P<0.05);且RAS( PRA、AngⅠ、Ang Ⅱ)与NAFLD的病情轻重程度呈正相关( P＝0.000);NAFLD组在治疗后与治疗前相比较其RAS、ALT、GGT、TG、TCHO、GLU差异均有统计学意义( P<0.05)。结论：血浆中RAS的变化可影响NAFLD的发生发展,并能改善NAFLD患者的生化指标,有利于病情的好转。     

滤过钠排泄分数在肾病综合征患者血容量评估中的作用

目的探讨滤过钠排泄分数(FeNa)对肾病综合征患者血容量评估的作用。方法将我院2010年10月至2011年6月期间住院的36例肾病综合征患者按照FeNa=0.2%为临界值分为2组即FeNa<0.2%组与FeNa≥0.2%组,比较2组血渗透压、尿渗透压、尿素氮、尿素氮/血肌酐、血红蛋白、24 h尿钠、24 h尿钾、肾素、血管紧张素Ⅰ、血管紧张素Ⅱ及醛固酮水平。结果与FeNa≥0.2%组比较,FeNa<0.2%组肾素、血管紧张素Ⅰ、血管紧张素Ⅱ、醛固酮及HB均显著升高(P<0.05),尿钠水平显著降低(P<0.01),提示可能存在血容量不足。FeNa与肾素、血管紧张素Ⅰ、血管紧张素Ⅱ、醛固酮、HB之间存在负相关但无明显统计学意义。结论 FeNa可以作为肾病综合征患者血容量评估的参考指标,FeNa<0.2%时患者为低血容量性水肿,治疗上可在扩容基础上利尿治疗;FeNa≥0.2%时患者为高血容量性水肿,治疗上可单独使用利尿剂治疗。     

Effects of oenethera biennis oil on plasma lipid, thromboxane A2 and angiotensin II of chronic renal insufficiency

Oenethera biennis oil was administered (6 g per day) in 23 chronic renal insufficiency patients over a 4 week period. Changes of serum creatinine, creatinine clearance, plasma lipid, renin activity, and angiotensin II, urinary thromboxane B₂ and 6-keto-prostaglandin F_1α were observed before and after the treatment. Results showed that after treatment, the creatinine clearance increased, serum total cholesterol, triglyceride and low density lipoprotein decreased, high density lipoprotein increased, plasma renin activity, angiotensin II and urinary thromboxane B₂ decreased significantly. The conclusion was that Oenethera biennis oil could improve the pathological process of renal diseases, and has beneficial effects on plasma lipid disorder and glomerular hemodynamics.     

The Angiotensin Infusion Test and Peripheral Venous Renin Activity

Forty hypertensive patients were studied to examine the assumption that the angiotensin pressor dose reflects endogenous renin activity. Peripheral renin activity was assayed by the method of Boucher et al.⁴ Sensitivity to the infusion of synthetic angiotensin II was determined as suggested by Kaplan and Silah.¹

Sixteen patients with essential hypertension with normal renal angiography required 3.8 ng. angiotensin/kg./min. to raise the diastolic pressure 20 mm. Hg. All but one were sensitive to angiotensin infusion of less than 5 ng./kg./min. Renin activity was normal in all except in one sensitive subject. Angiotensin infusion response and mean renin activity in 13 patients with essential hypertension with abnormal renal angiography were similar to that of the first group. The pressor dose in 11 renovascular hypertensives was 9.8 ng./kg./min. All but three had elevated plasma renin activity.

Our results suggest that: (1) the angiotensin infusion test is suitable for differentiating patients with true renovascular hypertension from those with essential hypertension with or without associated renal artery disease; (2) the angiotensin pressor dose correlates with the level of peripheral venous renin activity (p < 0.01).

     

Effects of Ligustricum Wallichii on acute nephrotoxicity induced by cyclosporine A in rats]

We investigated the influence of cyclosporine A (CsA) on renal function, renin-angiotensin system (RAS) and platelet aggregation in addition to the effect of Ligusticum Wallichii (LW) on CsA actions in SD rats. Infusion of CsA (50 mg/kg, iv) resulted in a significant fall in glomerular filtration rate (GFR) and renal plasma flow (RPF) and a significant increase of plasma renin activity (PRA), angiotensin II (A II) level and percentage platelet aggregation. At the same time, treatment with 20% LW (8 ml/kg, iv) before CsA infusion significantly prevented the decline of GFR and RPF as well as the enhancement of platelet aggregation, but had no influence on CsA-mediated RAS activation. These results suggested that LW may be beneficial to the acute nephrotoxicity induced by CsA.     

Role of angiotensin II in the pathogenesis of hyperdipsia in chronic renal failure

The relation of thirst to the renin-angiotensin system was examined in 38 patients with chronic renal failure receiving hemodialysis treatment. They were classified into three groups, ie, group 1 (19 patients), no or modest thirst; group 2 (13 patients), moderate thirst; and group 3 (six patients), excessive thirst. The plasma renin activity, plasma angiotensin II levels, and interdialytic weight gains of groups 1 to 3 significantly increased in a progressive manner with intensity of thirst. The hyperdipsia experienced by four patients in group 3 ameliorated after administration of an angiotensin-converting-enzyme inhibitor. The hyperdipsia of some patients with chronic renal failure therefore appears to be mediated by increased production of endogenous angiotensin II.     

Plasma leucine enkephalin and beta-endorphin levels in patients with essential hypertension and the effects of captopril

To further study the relationship between endogenous opioid peptides and essential hypertension, we measured the concentrations of plasma leucine-enkephalin (LEK) and beta-endorphin (beta-EP) in 50 patients with essential hypertension by radioimmunoassay and investigated the effects of captopril on them. It was shown that the concentrations of plasma LEK and beta-EP in patients with essential hypertension were lower than those in normotensive subjects. No effects of age and sex were found on the concentrations of plasma LEK and beta-EP, and there was no difference in plasma LEK and beta-EP levels between patients with Stage I essential hypertension and those with Stage II essential hypertension. After a single dose of captopril, blood pressure and plasma angiotensin II decreased, plasma renin activity increased; and plasma LEK and beta-EP levels increased. Plasma LEK and beta-EP levels in patients with essential hypertension increased after one month of captopril treatment. In conclusion, the lower plasma LEK and beta-EP levels in patients with essential hypertension indicate that LEK and beta-EP may play a role in the pathogenesis of essential hypertension, and the depressor effects of captopril may act through LEK and beta-EP, besides blocking formation of angiotension II.     

Aldosterone and renin in essential hypertension.

A review of some recent laboratory findings indicates definite disturbances in aldosterone metabolism and regulation in patients with mild essential hypertension: (a) a significant mean increase in plasma aldosterone concentration in patients with mild and stable essential hypertension, in contrast to the absence of any difference in patients with labile borderline essential hypertension when in a normotensive phase, compared with control subjects; and (b) a significant mean decrease in metabolic clearance rate of aldosterone, associated with a 12% decrease in hepatic blood flow and an increased binding of aldosterone to a transcortin-like plasma globulin. The secretion rate of 18-hydroxy-11-deoxycorticosterone is above the upper range of normal in 60% of patients with mild, uncomplicated essential hypertension. The incidence of low-renin hypertension, when age and race are taken into account, is much lower than previously assumed. Unless measurements are repeated over a long period, one or two low values of plasma renin cannot be considered a permanent marker indicating a special category of patients with essential hypertension. Tonin, a new enzyme discovered by Boucher, which forms angiotensin II directly from a plasma protein, from the tetradecapeptide substrate and from angiotensin I, is present in most tissues, but in highest concentration in the submaxillary gland. This enzyme is under the control of beta-adrenergic receptors.     

Controlled trial of enalapril in patients with chronic fluid overload undergoing dialysis

About one third of patients receiving dialysis for end stage renal failure have chronic fluid overload despite advice to restrict their oral fluid intake. To investigate the potential of an angiotensin converting enzyme inhibitor in reducing the urge to drink and consequent gain in weight, a double blind, placebo controlled crossover trial of enalapril was conducted in 25 patients receiving dialysis who had fluid overload. The trial comprised a baseline period of four weeks; two periods of treatment, each of four weeks, during which patients received either placebo or enalapril 5 mg twice each week; and a follow up period of four weeks. Five patients withdrew from the trial, one because of an adverse drug reaction to enalapril. A range of biochemical and behavioural variables was measured during the baseline period, at the completion of periods 1 and 2, and during follow up. These variables included gain in weight between dialysis sessions; blood pressure; plasma concentrations of sodium, angiotensin II, and vasopressin; plasma renin and angiotensin converting enzyme activities; osmolality; and estimations of thirst, intake of fluid, and control of drinking. Enalapril caused a significant reduction in gain in weight between dialysis sessions, thirst, and oral intake of fluid in parallel with significantly increased renin activity, significantly decreased angiotensin converting enzyme activity, and decreased concentrations of angiotensin II. Gain in weight and angiotensin converting enzyme activity returned to baseline values once patients stopped taking enalapril. These results suggest that enalapril may act on the renin-angiotensin system and reduce intake of fluid by inhibiting angiotensin converting enzyme.     

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.     

Effect of stilboestrol on sodium balance, cardiac state, and renin-angiotensin-aldosterone activity in prostatic carcinoma

A prospective study examined the sequential effects of diethylstilboestrol (stilboestrol) on sodium balance, cardiac state, and renin-angiotensin-aldosterone activity in six patients with metastatic carcinoma of the prostate. Whereas metabolic balance studies did not show evidence of sodium retention during the first seven days of treatment, there was a significant and progressive increase in plasma volume after three months (mean increase 541 ml; p less than 0.01). Stilboestrol increased supine plasma renin and angiotensin II values but the response of renin-angiotensin-aldosterone activity to erect posture was progressively reduced during treatment. No significant changes in blood pressure or indices of cardiac function occurred during the three months of observation. The findings of increased basal renin-angiotensin-aldosterone activity and an increase in plasma volume suggest an important mechanism of the cardiac complications associated with oestrogen treatment.     

Intrarenal activation of renin angiotensin system in the development of cyclosporine A induced chronic nephrotoxicity

Background The relationship between cyclosporine-induced chronic nephrotoxicity （CAN） and renin-angiotenein II in humans is still contradictory. This study was conducted to detect the levels of renin and angiotensin II （ANGII） both in renal tissue and plasma from kidney transplantation patients suffering from CAN.
Methods Twenty-six patients with allograft biopsy-proven CsA-related chronic nephrotoxicity （CAN group） and chronic rejection （control group） were enrolled in this study. Renal tissues were subjected to immunohistochemical staining with renin and ANGII antibodies. Renin and ANGII plasma levels were measured when the biopsy was performed. The relationship between expression of renin or ANGII and clinicopathological manifestations were also investigated. The cyclosporine plasma level was obtained 2 hours after morning dose （C2）. In vitro, human umbilical vein endothelial cells （HUVEC） and rat mesangial cells （MC） were incubated with different concentrations of CsA （0, 250, 500, 1000 μg/L） for 24 hours. Secretion and expression of renin and ANGII was measured by radioimmunoassay or immunohistochemical staining.
Results Renal pathological scores for renin and ANGII expression were significantly higher in specimens of CAN than in controls （P 〈0.05）. The plasma levels of renin, ANGII and C2 in the CAN group were higher than the control group, but no significant difference was found （（0.37±0.12） ng·ml^-1·h^-1 vs （0.20±0.10） ng·ml^-1·h^-1, P=0.076; （122.69±26.73） pg/ml vs （121.88±36.35） pg/ml, P=0.977; （719.04±55.89） ng/ml vs （658.80±90.78） ng/ml, P=0.196, respectively）. In vitro, renin as well as ANGII expression increased significantly in both HUVEC and MC after the cells were incubated with CsA for 24 hours （P 〈0.05）. CsA also stimulated the secretion of ANGII in HUVEC and MC in a dose-dependent manner.
Conclusions Renal allograft biopsy is important to differentiate chronic CsA-related nephropathy from chronic rejection     

血浆血管紧张素Ⅱ高压液相层析—放射免疫结合技术测定及巯甲丙脯酸抑制其生成的研究

血浆血管紧张素Ⅱ(PATⅡ)经 Sep-pakC~(18)柱和高压液相层析(HPLC)分离,放射免疫(RIA)测定。并通过8例原发性高血压病人进行了巯甲丙脯酸抑制 PATⅡ生成的研究。结果显示,口服25mg 巯甲丙脯酸后10分钟,PATⅡ水平即有显著下降(P<0.01),60分钟时达最低水平(P<0.02)。平均动脉压(MAP)亦同时达到最低水平(P<0.02)。下降率为34%。60分钟后,APTⅡ,MAP 均逐渐回升。血浆肾素活性(PRA)在用药后30分钟内未见显著性变化。PRA水平反馈增高,但与 MAP 变化无同时达到峰值的相应关系。