Deterioration of renal function in hypertensive patients with scleroderma despite blood pressure normalization with captopril

Summary The orally active angiotensin-converting enzyme inhibitor captopril was administered for up to 11 weeks to three patients with progressive systemic sclerosis presenting with hypertension and plasma creatinine levels of 3.1, 7.2 and 10.4 mg/100 ml. Only one patient had malignant phase hypertension. In this patient a diuretic had to be added to captopril in order to keep blood pressure under control. Despite sustained blood pressure control during captopril administration, renal function deteriorated and hemodialysis treatment had to be started in all patients. Up to that time no substantial improvement in skin lesions was observed. During the period of dialysis, blood pressure was normal in all patients even though administration of captopril was discontinued. All three patients died of respiratory failure while on chronic hemodialysis for 3 to 4 weeks. These observations confirm that angiotensin-converting enzyme inhibition may be helpful in controlling blood pressure of patients with scleroderma. However, in contrast to some earlier reports, they also indicate that converting enzyme inhibition does not always prevent the multivisceral vascular lesions of scleroderma.This study was supported in part by grant Nos. 3.914.080 and 3.824.081 of the Swiss National Science Foundation     

Minoxidil and captopril in severe hypertension

Summary The antihypertensive efficacy of minoxidil and captopril was compared in 23 males with essential or renal parenchymatous hypertension refractory to conventional antihypertensive drug therapy. Following a pretreatment period the patients were randomly assigned to receive either minoxidil, 2.5 mg twice daily (n=12), or captopril, 25 mg twice daily (n=11). In patients with diastolic blood pressure >95 mmHg, doses of minoxidil and captopril were increased in 2-week intervals. Patients who maintained diastolic pressure >95 mmHg and/or those with intolerable side effects were switched over to the alternative substance. After a mean observation period of 12 weeks a significant decrease in systolic and diastolic blood pressure was observed (179/114 vs 148/92 mmHg in the minoxidil group; 176/111 vs 158/97 mmHg in the captopril group). The primary response rate was 75% in patients treated with minoxidil and 55% in those with captopril (not significant). After the change to the alternative substance two of the four non-responders on captopril and one of the two non-responders on minoxidil became responders. Side effects occurred significantly more often during minoxidil than captopril (p<0.05). The high efficacy of minoxidil and captopril in the treatment of severe hypertension refractory to conventional drugs was confirmed. Minoxidil lowered blood pressure slightly more than captopril, but it had a higher incidence of side effects than captopril.     

Effect of captopril on heavy proteinuria in azotemic diabetics

We investigated whether captopril, an angiotensin-converting-enzyme inhibitor, would reduce proteinuria in patients with advanced diabetic nephropathy. Captopril (37.5 mg given in divided doses three times daily) was administered to 10 azotemic diabetics with heavy proteinuria. Urinary protein decreased promptly within two weeks (from 10.6 +/- 2.2 to 6.1 +/- 1.4 g per day [mean +/- S.E.M.]; P less than 0.01). The decrease in proteinuria did not coincide with a fall in systemic blood pressure or in the blood glucose concentration. Serum creatinine and potassium values did not change in any of the patients except one. We suggest that captopril caused a decrease in intrarenal hypertension, which contributed to the reduction of urinary protein excretion. The therapeutic value of this intervention remains to be established.     

Captopril in severe preeclampsia

Captopril is an inhibitor of angiotensin I converting enzyme and is used for treating intractable chronic hypertension. However, the use of captopril during pregnancy is limited because of reported fetal and neonatal side effects. This study explored the efficacy of sublingual captopril in postpartum management of severe preeclampsia. Captopril controlled the systolic and diastolic pressures within normal range in two patients. The other three patients responded moderately and were switched to hydralazine, clonidine, or nifedipine after 12 hours. The systolic and diastolic pressures of these three patients remained moderately elevated over the 24-hour duration of the study while their pulse rates increased. Captopril did not significantly increase the pulse rate in any of the patients studied, and no other side effects were noted. All patients had normal pressures at their 2- and 6-week postpartum check-up. We conclude that sublingual captopril may be used safely and effectively in managing postpartum hypertension in patients with severe preeclampsia.     

Studies of the renal component of the hypertension in rats with aortic constriction. Role of angiotensin II

The object of this study was to investigate the renal component of hypertension in aortic constriction. In 40-day-old Sprague-Dawley rats the aorta were constricted either proximal (PAC) or distal (DAC) to the renal arteries. The rats were examined 3 weeks later together with control rats. The arterial pressure proximal to the constriction was elevated in the PAC group but not in the DAC group. In PAC rats the arterial pressure was also elevated distal to the constriction. There was a significant pressure gradient across the constriction in both PAC and DAC rats. The PAC rats had a significant decrease of renal blood flow, a significant increase in renal vascular resistance and a numerical but not significant decrease of glomerular filtration rate. Serum levels of angiotensin II were not significantly different in PAC and control rats. The pressor effect of a bolus dose of angiotensin II was significantly increased in PAC rats. Captopril, a converting enzyme inhibitor, decreased the arterial pressures and renal vascular resistance in PAC rats. The pressure elevating effects of angiotensin II and pressure lowering effect of captopril were more pronounced distal than proximal to the constriction. We conclude that the kidneys play a major role in the development of hypertension in PAC, and that the local effect of angiotensin II on the renal vascular bed is an important contributor to the renal component of the hypertension.     

Effect of captopril on heavy proteinuria in patients with various glomerular diseases.

The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p < 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p < 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven.     

Converting enzyme inhibition in mild and moderate essential hypertension. II

In 24 patients with mild/moderate essential hypertension, we studied the effects of captopril with/without hydrochlorothiazide (Htz) on blood pressure, the renin-angiotensin system, blood bradykinin concentration (BBK), plasma volume, exchangeable sodium and glomerular filtration. Daily captopril doses of 75 and 150 mg were equally effective in reducing the blood pressure. Addition of Htz caused further blood pressure reductions. Nineteen patients attained a diastolic blood pressure less than or equal to 90 mmHg. Angiotensin converting enzyme inhibition with captopril led to a fall in plasma concentrations of angiotensin II (PAII) and renin substrate, and an increase in plasma concentrations of renin and angiotensin I. Patients starting with Htz had a higher PAII and subsequently a larger fall in blood pressure on captopril than untreated patients. BBK remained unchanged, indicating that the hypotensive action of captopril does not involve an accumulation of circulating kinin. Body fluid volumes and renal function were not affected by the various treatment regimens.     

Beneficial effect of captopril on systemic lupus erythematosus-like disease in MRL lpr/lpr mice

MRL lpr/lpr (MRL/l) mice exhibit a disease similar to systemic lupus erythematosus (SLE) in humans. To investigate the influence of antihypertensive treatment on this disease, four groups of MRL/l mice were treated with the angiotensin-converting enzyme inhibitor captopril (n = 25), with the sympathetic blocker bretylium (n = 15), and with cyclophosphamide (n = 10). Thirty-five mice did not receive any treatment and served as controls. Survival rate, blood pressure, incidence of proteinuria and hematuria, renal pathology, lymphoid hyperplasia and dermatitis were studied. The survival at the age of 36 weeks was significantly improved by captopril as compared to controls (60 vs. 25%, p = 0.035). The cyclophosphamide group showed no mortality at that time and the bretylium group did not differ from the control group. Captopril and bretylium reduced systolic blood pressure significantly while cyclophosphamide was without effect. Captopril and cyclophosphamide diminished significantly the glomerular damage with less proliferative changes and a decreased incidence of proteinuria. The bretylium-treated animals also exhibited an improved renal pathology index but they did not differ from the controls with respect to proteinuria and hematuria. Lymphoid hyperplasia and dermatitis were decreased only by captopril and cyclophosphamide. It is concluded that captopril improves survival in SLE disease of MRL/l mice, counteracting lymphoid hyperplasia, renal disease, dermatitis and decreasing arterial blood pressure.     

No effect of intrarenal converting enzyme inhibition on canine renal blood flow

Captopril and teprotide were administered intra-arterially to the kidney and intravenously to inhibit intrarenal and extrarenal converting enzyme (CE), respectively. Captopril was infused at 0.4, 0.8, and 1.6 micrograms . kg-1 . min-1 intra-arterially, and teprotide was given at 0.4 and 0.8 micrograms . kg-1 . min-1 intra-arterially in salt-replete dogs (group 1). Both agents were also given intravenously in the dose of 0.2 mg/kg, known to cause maximal extrarenal CE inhibition. The intra-arterial infusions of the inhibitors had no effect on renal hemodynamics but caused a graded degree of intrarenal CE inhibition. A lesser degree of extrarenal CE inhibition was seen after captopril in these doses. Intravenous administration of captopril and teprotide inhibited extrarenal CE, but only captopril increased renal blood flow (13%). When teprotide was given in a higher dose (group 3, 1.02 mg/kg), it too increased renal blood flow. In salt-deplete dogs (group 2), captopril infused intra-arterially caused a degree of intrarenal CE inhibition comparable with that in the salt-replete dogs but again produced little or no renal hemodynamic changes. When given intravenously in this group, captopril inhibited extrarenal EE and elicited a greater increase in renal blood flow (36%) than in the group 1 dogs. These results indicate that in conscious dogs renal vasodilatation is associated with extrarenal, but not intrarenal, CE inhibition.     

Long-term effect of captopril on kidney function in various forms of hypertension

Summary To study long-term effects of captopril on renal function in patients with various forms of severe hypertension, serum creatinine values were monitored in 76 patients under captopril therapy over a period of up to 3 years. Three different groups were formed: (1) patients with essential hypertension (n=37); (2) patients with renovascular hypertension (n=20); (3) patients with renal parenchymatous hypertension (n=19). In each of the three groups reduction in blood pressure was accompanied by increases in serum creatinine. However, both changes were more pronounced in patients with renovascular hypertension. In this group only the rise in creatinine was statistically significant and showed a slight progression with duration of captopril treatment. Group specific analysis revealed that the increase was smaller in patients with unilateral (n=16) renovascular disease than in those with bilateral (n=4) involvement, but in the former it was still significantly higher than in patients with essential or renal parenchymatous hypertension. Separation of patients according to the underlying disease of renovascular hypertension showed that renal function deteriorated less in patients with arteriosclerotic origin (n=10) than in those with fibromuscular dysplasia (n=8). Statistical evaluation of subjects with renovascular and essential hypertension still revealed significant differences in creatinine when the patients with initial plasma renin activity (PRA) below and above 6 ng/ml·3 h were compared separately. A significant correlation (r=0.73;P<0.05) between blood pressure reduction and creatinine changes was obtained only for patients with renovascular hypertension. Finally, in all three groups of patients creatinine changes were statistically independent from daily dosages of captopril. From these data we conclude that sustained impairment of kidney function by captopril is mainly restricted to patients with renovascular hypertension and possibly results from the combined effects of low renal perfusion pressure and interference with intrarenal regulation of glomerular filtration rate by a postulated angiotensin-II-mediated mechanism.Dedicated to Prof. W. Siegenthaler on the occasion of his 60th birthday     

Role of angiotensin-II in the polydipsia of diabetes insipidus in the Brattleboro rat

Captopril, an inhibitor of angiotensin converting enzyme which prevents conversion of angiotensin I (AI) to angiotensin II (AII), reduces the polydipsia of Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI). In the present study, captopril (480 mg/kg-day) reduced DI polydipsia by 18% with no change in plasma osmolality; an equivalent (17%) reduction caused by quinine (0.02%) adulteration of drinking water increased plasma osmolality significantly. If captopril reduces water intake of DI rats because it removes a dipsogenic signal to the CNS, plasma osmolality should have increased during captopril treatment. Captopril probably reduces DI polydipsia because it reduces renal water loss by lowering blood pressure. Both furosemide and spironolactone, which reduce renal water loss and increase AII levels, also reduced DI polydipsia with no change in plasma osmolality. Thus, only a small fraction of DI polydipsia seems to be controlled by a dipsogenic effect of AII.     

Effects of the converting enzyme inhibitor captopril on blood coagulation and fibrinolysis in man

Summary Systematic blood coagulation analyses were conducted in 32 severely hypertensive patients treated with the angiotensin converting enzyme inhibitor captopril. Two hours after the first captopril dose, fibrin monomer complexes had already increased. This rise was even more distinct after 26 h and 1 week. Tests after 6 and 12 months of therapy showed a regression of fibrin monomer complexes to pretreatment values. In several patients with a marked increase in fibrin monomer complexes, the partial thromboplastin time (PTT) became shorter and antiplasmin activity increased. The most pronounced increase in fibrin monomer complexes was seen in patients with a rapid and excessive blood pressure reduction.The concentration of fibrin monomer complexes also rose in 15 healthy normotensive subjects, after a single oral dose of captopril (25 mg). Additionally, the PTT was shortened and antiplasmin significantly rose. An inhibition of fibrinolysis by captopril could be demonstrated by the effect on fibrin plates and thrombus weight after streptokinase. Out of 58 patients with severe hypertension and atherosclerosis treated with captopril, 7 patients suffered vascular complications during antihypertensive therapy: myocardial infarction (n=2), coronary insufficiency (1), cerebral ischemia (1), renal insufficiency (3). These ischemic lesions may be partly explained by the alterations of coagulation and fibrinolysis under captopril therapy.Dedicated to Prof. Dr. H.-J. Bretschneider on the occasion of his 60th birthday     

Angiotensin-converting enzyme inhibitor captopril prevents activation-induced apoptosis by interfering with T cell activation signals

Captopril is an orally active inhibitor of angiotensin-converting enzyme (ACE) which is widely used as an anti-hypertensive agent. In addition to its ability to reduce blood pressure, captopril has a number of other biological activities. Recently the drug was shown to inhibit Fas-induced apoptosis in human activated peripheral T cells and human lung epithelial cells. In this study, we investigated whether captopril blocks activation-induced apoptosis in murine T cell hybridomas, and found that captopril inhibited IL-2 synthesis and apoptotic cell death upon activation with anti-CD3 antibody. In addition, captopril inhibited an inducible caspase-3-like activity during activation-induced apoptosis. On the other hand, captopril did not interfere with Fas signalling, since anti-Fas antibody-induced apoptosis in Fas+ Jurkat cells was unaffected by the drug. Furthermore, we examined whether captopril blocks activation-induced apoptosis by interfering with expression of Fas, Fas ligand (FasL), or both on T cell hybridomas. FasL expression on activated T cells was significantly inhibited by captopril, whereas up-expression of Fas was partially inhibited, as assessed by cell surface staining. Taking all data together, we conclude that captopril prevents activation-induced apoptosis in T cell hybridomas by interfering with T cell activation signals. Captopril has been reported to induce systemic lupus erythematosus syndrome, and our findings may be useful for elucidating the mechanism of captopril-induced autoimmunity.     

Captopril in various forms of severe therapy-resistant hypertension

Summary In this study 51 patients with severe hypertension (20 essential, 15 renovascular and 16 renalparenchymatous) resistant to a standardized triple therapy were treated with the oral converting enzyme inhibitor captopril. Mean treatment period was 8.6 in essential, 8.9 in renovascular and 9.9 months in renalparenchymatous hypertension.In each of the 3 groups a marked and sustained blood pressure reduction was observed promptly after introducing captopril. However, absolute fall in mean blood pressure as well as individual blood pressure response were more pronounced in renovascular than in essential and in renalparenchymatous hypertension demonstrating a higher blood pressure lowering activity of the converting enzyme inhibitor in the former.In addition, our results document that monotherapy with captopril was rather the exception than the rule. More than 90% of all patients required at least the addition of a diuretic and even a substantial percentage of patients needed as a third drug a betablocker (50% in essential, 38% in renalparenchymatous and 26% in renovascular hypertension).As expected renin activity increased under captopril whereas plasma aldosterone and converting enzyme activity decreased.Side-effects (skin rash, pruritus, supraventricular extrasystoles, tachycardia, water and fluid retention, Raynaud-phenomenon, incomplete and complete taste loss and leucopenia) occurred in 17.6% (n=9) of the 51 patients.Our results show that captopril is a potent blood pressure lowering agent in severe and therapy resistant hypertension. The vast majority of patients, however, required concomitant therapy with a diuretic and/or a betablocker. Finally, the frequency of drug induced side-effects necessitates a close and careful monitoring of all patients.     

高血压胰岛素抵抗与内皮素的相关性及其干预治疗

探讨内皮素与高血压胰岛素抵抗的相关性和卡托普利加左旋氨氯地平对高血压患者胰岛素抵抗的改善作用.选择在本院内科就诊的25例原发性高血压伴糖耐量异常患者,使用卡托普利加左旋氨氯地平联合用药治疗,在治疗前与治疗后测量收缩压、舒张压,测定空腹血糖、胰岛素、胰岛素抗体和胰岛素抵抗指数的变化.对照组21例为体检健康人群.高血压组血...     

巯甲丙脯酸和倍他乐克对高血压大鼠左心室MHC基因表达的影响

目的和方法：采用核酸斑点杂交技术,测定双肾双夹（2K2C）肾性高血压大鼠早期左心室肌球蛋白重链（MHC）基因表达的变化,及血管紧张素转换酶抑制剂巯甲丙脯酸和β-受体阻断剂倍他乐克对该变化的影响。结果：2K2C组大鼠术后24 h,左心室α-MHCmRNA水平即有所降低,72 h时明显降低,为对照组的0.48倍（P<0.05）;与此相反,2K2C组β-MHC mRNA水平,在术后24 h已略有升高,72 h时明显增加,为对照组的2.7倍（P<0.05）。巯甲丙脯酸可抑制2K2C引起的MHC基因表达的改变,而倍他乐克不能阻止该变化。结论：肾性高血压早期,MHC基因表达发生改变,肾素血管紧张素系统可能起重要作用。     

Der Stellenwert des Captopriltests in der Hypertoniediagnostik

Summary The place of captopril (C) testing in the screening for renovascular hypertension is still controversial. Baseline and C-stimulated plasma renin concentrations (PRC) were measured in 113 hypertensives, who where referred for the exclusion of secondary hypertension. In addition intravenous digital subtraction angiography (DSA) and a renal scintigraphy were performed. When renal artery disease was revealed by DSA or renin was stimulated the renal arteries were visualized by direct arteriography (and treated by angioplasty if possible). 86 patients underwent each diagnostic test: 21% had renovascular hypertension. Unilateral renal artery stenosis (n=10) was detected by the captopril test (cutoff values: baseline>40 µU/ml, after C>180 µU/ml, sensitivity 100%). Bilateral renal artery stenosis (n=8) was missed when the disease was equally severe on either side (sensitivity 50%). The specificity of C testing was 82%, overall sensitivity (uni- and bilateral disease 78%, prevalence 21%, predictive value of the positive test 0.56, predictive value of the negative test 0.93). With i.v.-DSA the renal arteries were technically evaluable in 91% (82/92) of cases. The sensitivity for the detection of all renal artery stenoses was 79% (unilateral 100%, bilateral 40%, specificity 97%). The sensitivity of renal scintigraphy for the detection of unilateral renal artery stenosis was 50%, for the detection of bilateral renal artery stenoses 43%, specificity 81%. The present study demonstrates the usefulness of captopril for the detection of unilateral renal artery stenosis. Since bilateral renal artery disease is frequent and frequently missed by the test, overall and split renal function should be evaluated in addition. Both tests can easily be combined at one time when a captopril scintigraphy with renin determination is performed.

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Abkürzungen C Captopril - DSA Digitale Subtraktionsangiographie - MAP Mittlerer arterieller Blutdruck - PRA Plasma Renin Aktivität - PRC Plasma Renin Konzentration - PTA Perkutane transluminale Angioplastie Herrn Prof. Dr. med. W. Kaufmann zum 65. Geburstag gewidmet     

The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group

BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood. METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function. CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.     

A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension

It has been suggested that the metabolic side effects of antihypertensive drugs are responsible for their failure to reduce cardiovascular morbidity in patients with hypertension. Therefore, in 50 patients with essential hypertension, we performed a randomized, double-blind, crossover study comparing the effects of carbohydrate and lipid metabolism of captopril (mean [+/- SD] dose, 81 +/- 24 mg per day) and hydrochlorothiazide (40 +/- 12 mg per day) over two four-month treatment periods. Captopril increased the insulin-mediated disposal of glucose, as compared with placebo, from 5.7 +/- 2.4 to 6.3 +/- 2.5 mg per kilogram of body weight per minute (P less than 0.05), whereas hydrochlorothiazide caused a decrease from 6.4 +/- 2.0 to 5.7 +/- 1.9 (P less than 0.01). Captopril had no effect on the basal insulin concentration, but it decreased the late (30- to 90-minute) insulin response to glucose and increased the early (2- to 6-minute) insulin peak. Hydrochlorothiazide increased the basal insulin concentration and the late insulin response to glucose. These findings may be explained by an increase in insulin sensitivity with captopril and a decrease with hydrochlorothiazide. Little or no change was seen in serum lipid or lipoprotein levels during treatment with captopril, whereas hydrochlorothiazide caused significant increases in serum total (5 percent) and low-density lipoprotein (6 percent) cholesterol levels and total (15 percent) and very-low-density lipoprotein (25 percent) triglyceride levels, as compared with placebo (P less than 0.01 for all comparisons). We conclude that hydrochlorothiazide for the treatment of essential hypertension has adverse effects on glucose and lipid metabolism. It is possible, but not proved in this study, that these changes may contribute to the risk for diabetes mellitus and coronary heart disease. In contrast, captopril appears to have beneficial or no effects on glucose and lipid metabolism.