Regression of left ventricular hypertrophy with moexipril, an angiotensin-converting enzyme inhibitor, in hypertensive patients

Left ventricular hypertrophy (LVH) is a common complication of essential hypertension and an independent risk factor for the development of cardiovascular disease. Therefore, antihypertensive treatment should decrease blood pressure (BP) and reverse LVH. However, antihypertensive drugs have been shown to have different effects on LVH despite similar effects on BP reduction. Although lowering BP produces a beneficial effect on LVH per se, meta-analyses of clinical trials have indicated that angiotensin-converting enzyme (ACE) inhibitors decrease left ventricular mass (LVM) to a greater extent than do some other antihypertensives. The aim of this study was to evaluate the effect of a 24-week treatment with the ACE inhibitor moexipril (15 mg once daily) on the regression of LVH in hypertensive patients. This was a multicenter, international, single-blind, single-group, nonrandomized study. After a wash-out placebo period of 2 weeks, 15 mg moexipril once daily was administered for 24 weeks followed by a 2-week follow-up placebo period. Subjects with mild to moderate essential hypertension were screened; those with LVH [defined as an LVM indexed for body surface area (LVMIs) >111 g/m in men and LVMIs >106 g/m in women] were eligible to participate in this study. Echocardiograms were recorded on videotape and sent to a centralized laboratory for reading by 2 independent experts blinded for treatment, center, and visit; the mean values of these readings were calculated and used for analysis. Valid echocardiographic data were obtained from 72 patients (50 males, 22 females) with a mean age of 49 +/- 11 years. Analysis showed significant decrease of LVMIs (121 +/- 20 versus 103 +/- 17 g/m; P < 0.001) and BP (152 +/- 12/96 +/- 9 versus 140 +/- 13/86 +/- 9 mm Hg; P < 0.001) with moexipril. For patients who met LVMI inclusion criteria after centralized, blinded readings, the decrease from baseline in LVMIs was 23.4 g/m. The decrease in LVMIs was independent from the regression to the mean phenomenon as observed from the follow-up placebo period. Moexipril 15 mg once daily administered for 24 weeks resulted in a significant reversal of LVH in patients with essential hypertension. The result compares favorably with results previously obtained in trials of similar duration with other ACE inhibitors.     

Temporal enhancement of renin-aldosterone blockade by enalapril, an angiotensin-converting enzyme inhibitor

Interruption of the renin-aldosterone system with angiotensin-converting enzyme inhibitors (CEI) should result in a low aldosterone secretion, but most investigators have measured aldosterone production only indirectly by plasma aldosterone (PA) levels or urinary metabolites. We evaluated the effects of CEI of the aldosterone secretion rate (ASR) and compared them with PA, urinary tetrahydroaldosterone (THA), plasma renin activity (PRA), and electrolyte balance in six normotensive subjects in a metabolic unit during a control period (5 days) and during administration of 10 mg/day enalapril for 28 days. Our results demonstrated that (1) the ASR did not decline until after 1 wk of CEI therapy and this was reflected by a corresponding decline in the urine potassium:sodium ratio, (2) upright PA levels at day 1 declined, but supine PA levels were unchanged, (3) THA excretion remained essentially unchanged and the THA:ASR ratio rose progressively during therapy, (4) PRA rose and was maximal on day 3, but subsequently declined. In conclusion, enalapril-induced hypoaldosteronism required several days to become demonstrable and this was not accurately assessed by PA or THA--possibly due, in part, to altered aldosterone metabolism. The simultaneous decline in both PRA and ASR could be due to a decrease in renin substrate. Caution is therefore warranted when assessing aldosterone secretion indirectly by either PA levels or urinary metabolites during CEI therapy.     

Brain angiotensin-converting enzyme activity in experimental hypertensive rats

Angiotensin-converting enzyme (ACE) activity was measured in six areas of the brain of normotensive and experimental hypertensive rats; one-clip, one-kidney (1-c, 1-k) and one-clip, two-kidney (1-c, 2-k) Goldblatt hypertensive (GH) rats. ACE activity was consistently high in the thalamus of normotensive and both 1-c, 1-k and 1-c, 2-k GH rats. However, the enzyme activity in the hypothalamus of 1-c, 2-k GH rats was significantly higher than that of normotensive rats, while there was no significant difference in the enzyme activity between normotensive and 1-c, 1-k GH rats. These results demonstrate that in 1-c, 2-k GH rats, increased ACE activity in the brain may play a central role in the hypertension.     

Inhibition of renal clearance of furosemide by pentopril, an angiotensin-converting enzyme inhibitor

The pharmacokinetic interaction between pentopril (250 mg) and furosemide (40 mg) was studied in 12 normal healthy volunteers after oral administration of each drug alone and in combination. No significant changes in any pharmacokinetic parameters of pentopril or its active metabolite (CGS 13934) were observed on coadministration of furosemide. In contrast, pentopril induced significant changes in disposition of furosemide. Pentopril decreased renal clearance (CLR) of furosemide by 54% and the fraction excreted unchanged in urine also decreased by 55%. However, such decrease in CLR of furosemide was compensated by a simultaneous increase in glucuronidation (by 200%), resulting in a slight increase in systemic clearance (decreased AUC). Systemic bioavailability of furosemide appears to be unchanged in the presence of pentopril (0.46 vs. 0.41). No effect of pentopril on plasma protein binding of furosemide was detected. In spite of the decreased CLR and urinary excretion rate of furosemide, the urinary output (1749 vs. 1774 ml/6 hr) and Na+ excretion (757 vs. 816 mEq/6 hr) remained almost unchanged. These findings suggest that total furosemide (unchanged and glucuronide) might contribute to diuresis and natriuresis rather than the unchanged furosemide alone. Because of unchanged pharmacodynamic effect, such pharmacokinetic interaction may not require any dosage adjustment for furosemide on pentopril coadministration.     

Effects of chronic administration of an angiotensin-converting enzyme inhibitor on angiotensin-converting enzyme activity in the pars recta of rabbits

1. To determine whether chronic angiotensin-converting enzyme inhibition induces a decrease in proximal tubular angiotensin-converting enzyme activity, urine and blood samples were collected in conscious New Zealand rabbits before and after 16 days administration in drinking water of low doses of captopril (2.6 +/- 0.6 mg 24 h-1 kg-1), high doses of captopril (7.6 +/- 0.9 mg 24 h-1 kg-1) or no captopril (controls). The kidneys were then removed and angiotensin-converting enzyme activity was determined in isolated pars recta of microdissected nephrons as pmol of tritiated hippurylglycylglycine substrate hydrolysed min-1 of incubation and mm-1 of tubule. 2. Both low and high doses of captopril significantly decreased plasma angiotensin-converting enzyme activity and increased plasma renin activity, thus indicating an effective inhibition of circulating angiotensin-converting enzyme. Both low and high doses of captopril also significantly decreased mean arterial pressure and increased water intake and urine flow rate. Neither dose modified creatinine clearance and absolute and fractional sodium excretion. 3. None of the doses altered urinary kallikrein excretion. Urinary excretion of kinins was increased by 98.7% compared with control rabbits by the high dose of captopril (402 +/- 152 vs 251 +/- 104 ng/24 h, P less than 0.01) but was unchanged by the low dose of captopril. 4. Angiotensin-converting enzyme activity in the pars recta was lower in rabbits given the high dose of captopril than in control rabbits (17.6 +/- 7.2 vs 37.3 +/- 9.0 pmol min-1 mm-1, P less than 0.01) but was not decreased in rabbits given the low dose of captopril (40.4 +/- 5.0 pmol min-1 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in essential hypertensive patients with left ventricular hypertrophy

Continuous angiotensin-converting enzyme (ACE) inhibitor therapy does not necessarily produce significant decreases in plasma aldosterone levels (aldosterone escape). We examined the role of aldosterone escape in 75 essential hypertensive patients treated with an ACE inhibitor (enalapril maleate [34 patients], imidapril hydrochloride [24 patients] or trandolapril [17 patients]) for 40 weeks. With treatment, blood pressure decreased and plasma renin activity increased, while plasma aldosterone concentrations did not change. Aldosterone escape was observed in 38 of the 75 patients and in 17 of 37 patients with left ventricular hypertrophy before treatment. Left ventricular mass index did not change in patients with aldosterone escape but decreased significantly in patients without aldosterone escape. The present study demonstrated a high incidence of aldosterone escape in patients with essential hypertension despite the use of ACE inhibitors. The results also suggest that aldosterone escape may reverse the beneficial effects of an ACE inhibitor on left ventricular hypertrophy.     

Trandolapril: a newer angiotensin-converting enzyme inhibitor

BACKGROUND: Trandolapril is a newer angiotensin-converting enzyme (ACE) inhibitor that is approved by the US Food and Drug Administration for the treatment of hypertension and for use in stable patients who have evidence of left ventricular (LV) systolic dysfunction or symptoms of chronic heart failure within the first 2 days after an acute myocardial infarction (AMI). The fixed-dose combination of trandolapril and verapamil extended release (ER) is approved for the treatment of hypertension only. OBJECTIVE: The purpose of this article was to review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of trandolapril as monotherapy and in fixed-dose combination with verapamil ER. METHODS: Relevant studies were identified through a MEDLINE/PubMed search of the English-language literature published between January 1983 and August 2002 and a review of the bibliographies of identified articles. RESULTS: Trandolapril has a sufficient duration of inhibition of plasma ACE activity to allow once-daily dosing. It is converted by esterases to the active trandolaprilat metabolite, with mean terminal disposition half-lives of < 1 and approximately 75 hours for the prodrug and metabolite, respectively. In comparative trials in the management of hypertension, trandolapril 1 to 4 mg/d was statistically indistinguishable from or superior to captopril 100 mg/d, enalapril 10 or 20 mg/d, hydrochlorothiazide (HCTZ) 25 mg/d, nifedipine ER 30 or 40 mg/d, nitrendipine 20 mg/d, perindopril 4 mg/d, and verapamil ER 120 to 240 mg/d. In the Trandolapril Cardiac Evaluation, trandolapril also significantly reduced all-cause mortality, cardiovascular mortality, sudden death, and progression to severe chronic heart failure in patients with evidence of LV systolic dysfunction after AMI. In comparative trials in the management of hypertension, the combination of trandolapril 1 or 2 mg/d and verapamil ER 180 mg/d was statistically indistinguishable from or superior to the combinations of atenolol 50 or 100 mg/d plus chlorthalidone 12.5 or 25 mg/d, captopril 50 mg/d plus HCTZ 25 mg/d, lisinopril 20 mg/d plus HCTZ 12.5 mg/d, and metoprolol 100 mg/d plus HCTZ 12.5 mg/d. The most common adverse effects of trandolapril monotherapy in clinical trials of < or = 1 year's duration included cough, dizziness, and diarrhea (frequency < or = 1.9%). The most common adverse effects of trandolapril/verapamil ER therapy in clinical trials of < or = 1 year's duration included first-degree atrioventricular block, bradycardia, constipation, cough, diarrhea, dizziness, fatigue, and dyspnea (frequency < or = 4.6%). Based on the literature search, there are no published pharmacoeconomic evaluations of trandolapril alone or combined with verapamil ER in the US health care setting. CONCLUSIONS: Based on the literature, trandolapril is a well-tolerated and effective antihypertensive agent, whether used alone or in combination with verapamil ER. These products may be valuable in patients with LV systolic dysfunction after AMI, although the combination product is approved for the management of hypertension only.     

Hemodynamic effects of quinapril, a novel angiotensin-converting enzyme inhibitor

The hemodynamic effects of quinapril, a novel nonsulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, were assessed in 10 patients with mild-to-moderate essential hypertension. Compared with placebo, quinapril (20 mg) administered twice daily for 4 weeks significantly lowered blood pressure by decreasing total peripheral resistance without producing tachycardia, an increase in cardiac output, or a rise in plasma catecholamines. Quinapril significantly reduced renal, but not forearm, vascular resistance. Renal blood flow, glomerular filtration rate, and filtration fraction remained unchanged. Left ventricular wall stress was markedly reduced by quinapril, but during the relatively short treatment period, only a nonsignificant trend toward reduction in left ventricular mass was observed. These findings suggest that quinapril is an effective antihypertensive agent that lowers peripheral resistance without increasing cardiac output or disturbing autoregulation of renal hemodynamics.     

Comparison of systemic and regional hemodynamic effects of a diuretic, an angiotensin II receptor antagonist, and an angiotensin-converting enzyme inhibitor in conscious renovascular hypertensive rats.

The present experiments were designed to compare the antihypertensive action and the systemic and regional hemodynamic effects of a diuretic (furosemide), an angiotensin II (AngII) receptor blocker (Dup 753), and an angiotensin converting enzyme (ACE) inhibitor (enalapril) in conscious, two-kidney, one-clip renovascular hypertensive rats by the radioactive microsphere technique. Measurements were done 3 hours after a single dose treatment. Furosemide (20 mg/kg) produced a marked diuresis and tachycardia with no change in blood pressure; in comparison with control rats, furosemide-treated rats had total peripheral vascular resistance increased by 46.55% (p less than 0.01) and local vascular resistance increased in most organs, to a significant degree in the spleen, muscle, stomach, intestine, and skin (p less than 0.05 to 0.01). Dup 753 (20 mg/kg) and enalapril (10 mg/kg) decreased mean blood pressure by 41.89 +/- 7.17 mm Hg and 47.13 +/- 8.67 mm Hg, respectively (p less than 0.01), with tachycardia only in the Dup 753 group. Total peripheral and local vascular resistances in several tissues were significantly lower in both the Dup 753 and enalapril groups than in the furosemide group. In particular, both antiangiotensin agents, in contrast to furosemide, produced significant decrease in renal vascular resistance by 42.28% and 38.81%, respectively (p less than 0.01), with a tendency to increase the renal blood flow (of the intact kidney). No detectable differences were found in systemic and regional hemodynamic changes between the Dup 753 and enalapril group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Visceral angioedema due to angiotensin-converting enzyme inhibitor therapy

Visceral angioedema is an uncommon but serious complication of therapy with angiotensin-converting enzyme (ACE) inhibitors. We report a case, review the literature, and discuss the incidence, features, and clinical recognition of this condition.     

Combined therapy with an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor in heart failure

OBJECTIVE: To evaluate the safety, tolerability, and efficacy of chronic combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) in the management of heart failure. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1966-June 2000). Key search terms included angiotensin-converting enzyme inhibitor; losartan; combined modality therapy; drug effects; heart failure, congestive; and receptors, angiotensin. DATA SYNTHESIS: Heart failure is widely prevalent and continues to be associated with high morbidity and mortality, even with currently recommended care. At the moderate doses studied for patients with mild heart failure in brief trials, combined ACE inhibitor and ARB therapy was well tolerated and had an additive effect in reducing blood pressure and relieving symptoms of heart failure. CONCLUSIONS: An ARB combined with an ACE inhibitor may benefit heart failure patients who are receiving all other recommended therapies. Further trials are needed to evaluate long-term safety effectiveness, quality of life, and survival before the combination can be recommended for routine use.     

Combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats

Cardiovascular risk factors are associated with reduction in both the number and function of vascular progenitor cells. We hypothesized that 1) hypertension abrogates postnatal vasculogenesis, and 2) antihypertensive treatment based on the combination of perindopril (angiotensin-converting enzyme inhibitor) and indapamide (diuretic) may counteract hypertension-induced alteration in progenitor cell-related effects. Postischemic neovascularization was significantly lower in untreated spontaneously hypertensive rats (SHRs) compared with Wistar Kyoto (WKY) rats (p < 0.05). Treatment of SHRs with perindopril and the combination of perindopril/indapamide reduced the blood pressure levels and normalized vessel growth in ischemic area. Cotreatment with perindopril and indapamide increased vascular endothelial growth factor and endothelial nitric-oxide synthase protein contents, two key proangiogenic factors. It is interesting to note that 14 days after bone marrow mononuclear cell (BM-MNC) transplantation, revascularization was significantly lower in ischemic SHRs receiving BM-MNCs isolated from SHRs compared with those receiving BM-MNCs isolated from WKY rats (p < 0.05). Alteration in proangiogenic potential of SHR BM-MNCs was probably related to the reduction in their ability to differentiate into endothelial progenitor cells in vitro. Furthermore, the number of circulating endothelial progenitor cells (EPCs) was reduced by 3.1-fold in SHRs compared with WKY rats (p < 0.001). Treatments with perindopril or perindopril/indapamide restored the ability of BM-MNCs to differentiate in vitro into EPCs, increased the number of circulating EPCs, and re-established BM-MNC proangiogenic effects. Therefore, hypertension is associated with a decrease in the number of circulating progenitor cells and in the BM-MNC proangiogenic potential, probably leading to vascular complications in this setting. The combination of perindopril and indapamide counteracts hypertension-induced alterations in progenitor cell-related effects and restores blood vessel growth.     

Effects of low-dose combination therapy with an angiotensin-converting enzyme inhibitor and a diuretic on flow-mediated vasodilation in hypertensive patients: a 6-month, single-center study

Background

Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a diuretic has been shown to be highly effective in hypertension. Clinical trials have demonstrated that ACE inhibitors may improve endothelial cell dysfunction in hypertension. However, the effectiveness of the combination treatment in endothelial cell dysfunction is unknown.

Objective

This study investigated the effects of a new low-dose combination, perindopril 2 mg plus indapamide 0.625 mg, on brachial artery flow-mediated vasodilation (FMD) and left ventricular diastolic function in hypertension.

Methods

Patients aged 18 to 75 with newly diagnosed stage I or II hypertension were eligible. Endothelium-dependent brachial artery FMD and endothelium-independent vasodilation were assessed at baseline. Patients were treated with oral perindopril 2 mg plus indapamide 0.625-mg tablets once daily for 6 months. FMD measurements were then repeated. Percentage changes in FMD from baseline to 6 months, as well as left ventricular diastolic function parameters (isovolumic relaxation time [IVRT] and mitral diastolic E-wave deceleration time [EDT]), indicated the effectiveness of the intervention.

Results

Twenty-nine Turkish patients were enrolled (17 women, 12 men; mean [SD] age, 54.5 [9.5] years [range, 38-75 years]). The mean (SD) baseline FMD was 7.00% (2.39%) (endothelial cell dysfunction) and increased significantly to 8.68% (2.78%) at 6 months (P = 0.02); FMD improved in 15 patients (51.7%). At baseline and 6 months of therapy, mean (SD) IVRT was 101.7 (12.4) ms and 95.5 (7.7) ms, respectively (P<0.001), and EDT was 234.7 (33.9) ms and 217.9 (25.6) ms, respectively (P<0.001).

Conclusions

In this small sample of hypertensive patients, a low-dose combination ACE inhibitor and diuretic significantly improved brachial artery FMD and left ventricular diastolic function. The improvement in FMD values was independent of the stage of hypertension. These findings suggest a relationship between improvement in endothelial cell function and diastolic function.     

Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals.

The frequency of the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been reported to be elevated in myocardial infarction and other patients. We therefore hypothesized that death rate of DD individuals should be increased in the population as a whole and this should be evident as a decrease in DD frequency with age. This hypothesis was tested in 118 Caucasian subjects who were already at high risk of cardiovascular events by having severe, early onset, familial hypertension (HT). A group of 196 age-, sex- and body mass index-matched normotensives (NTs) was used as a control. In the NT group II, ID, and DD genotype frequencies were similar for different age groups. DD frequency was 0.42 in NTs, but in HTs was 0.28, 0.26, and 0.10 for the age groups < 50, 50-59, and > or = 60 yr, respectively. Corresponding D allele frequencies were 0.52, 0.46, and 0.40 in the respective age groups of HTs, compared with 0.61 in NTs (by chi 2-analysis, P = 0.1, 0.047, and 0.0006, respectively). In HTs aged > or = 60, DD frequency was only 14% of expected. Plasma ACE activity tracked similarly with I/D genotype in HTs (P = 0.027; n = 35) as in NTs (P = 0.0001; n = 94) and Michaelis constant was identical for DD and II. Neither blood pressure, body mass index, nor sex bore any relationship with I/D genotype. In conclusion, in a group of severely HT patients not selected for cardiac pathology, there appeared to be a marked, selective decrease, in subgroups of increasing age, in frequency of the ACE DD genotype. One possibility suggested by this data might be that DD increases risk of premature death, at least in HTs who have two HT parents.     

Amyotrophic lateral sclerosis with an acute hypertensive crises

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving the systemic motor neurons, but autonomic nervous function is relatively well preserved. A few studies related to autonomic dysfunction have been reported, but autonomic dysfunction is rare in ALS. Moreover, dysautonomia symptoms are not prominent in patients with ALS. We present a 55-year-old male patient with ALS, who had acute severe hypertension and tachycardia crises, as well as sudden falls in his blood pressure. After he was diagnosed with ALS, he suddenly collapsed and was placed under mechanical ventilation. Several hypertensive attacks and dysautonomic signs then occurred. We successfully controlled the dysautonomia using diazepam and doxazocin mesylate, an alpha receptor antagonist.     

Renovascular disease and renal complications of angiotensin-converting enzyme inhibitor therapy

Renal complications of angiotensin-converting enzyme (ACE) inhibitor therapy are widely recognized, but few authors have documented the incidence or spectrum of these conditions. In a retrospective study of 530 consecutive patients presenting to our unit as acute uraemic emergencies over a six-year period, 85 (16 per cent) had renovascular disease that was considered to be responsible for their loss of renal function. Twenty-one (4 per cent) patients had uraemia which could be clearly attributable to ACE inhibitor treatment; 18 of these cases were shown to have significant renovascular pathology. Following withdrawal of the ACE inhibitor the renal failure reversed in the majority of patients. We also examined 400 consecutive hypertensive patients referred over a similar period and, although vascular imaging was performed only when it was considered to be clinically indicated, 58 (14.5 per cent) of these patients were shown to have renovascular pathology. A further five patients with stable chronic renal disease were seen to have a deterioration in their glomerular filtration rate coincident with commencement of ACE inhibitor therapy; this reversed when the agents were withdrawn. These observations indicate that significant renovascular disease may be more common than has been hitherto recognized and that injudicious use of ACE inhibitors may result in serious complications. Methods which may minimize such iatrogenic disease are suggested.     

Combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker synergistically suppresses chronic pancreatitis in rats

We recently demonstrated that both lisinopril and candesartan, an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, respectively, attenuate pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori (WBN/Kob) rats. The purpose of the present study was to assess whether combination therapy with low doses of both, ineffective when given alone, might synergistically exert protective effects. Lisinopril, candesartan, or a combination of both in drinking water was administered to 10-week-old male WBN/Kob rats for 10 weeks. Parameters of inflammation and fibrosis, positive immunostaining for alpha-smooth muscle actin, and gene expression of cytokine and growth factors were assessed, as well as circulating renin-angiotensin system components. Dose-dependent effects of combination therapy were also investigated. Only combination therapy attenuated gross alterations in the pancreas, as quantitatively confirmed by increases in pancreatic weights and decreases in myeloperoxidase activity, hydroxyproline content, histologic scores, relative fibrosis area, and relative area of alpha-smooth muscle actin-positive cells. Combination therapy suppressed up-regulation of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA in the pancreas. Dose dependence of combination therapy was recognized with reference to improvement in these parameters. The conclusions are that combination therapy synergistically alleviated pancreatic inflammation and fibrosis in male WBN/Kob rats. This effect may be related to suppression of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA. Compared with the either therapy alone, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker may be more beneficial for treating chronic pancreatitis.     

Effect of sodium intake on brain angiotensin-converting enzyme activity in spontaneously hypertensive rat

The effect of sodium intake on angiotensin-converting enzyme activity in five areas of the brain (the cerebral cortex, midbrain, striatum, thalamus and hypothalamus) was studied in normotensive, spontaneously hypertensive and stroke-prone spontaneously hypertensive rats. The enzyme activity was significantly higher in the hypothalamus than in other areas of the brain of spontaneously hypertensive rats. Sodium intake resulted in a significant rise of the enzyme activity in the midbrain of spontaneously hypertensive rats and also in the midbrain and the striatum of stroke-prone spontaneously hypertensive rats. In normotensive rats, however, there was no significant difference in the enzyme activity in any area of brain between the control and the salt-treated group. It is likely therefore that a high circulating sodium level increases angiotensin-converting enzyme content of the brain in spontaneously hypertensive rats, and it is suggested that the increased converting-enzyme activity may play a role in development of hypertension induced by sodium loading.     

Antioxidant and cardioprotective properties of the sulphydryl angiotensin-converting enzyme inhibitor zofenopril

Zofenopril, a new potent sulphydryl angiotensin-converting enzyme (ACE) inhibitor, is characterized by high lipophilicity, selective cardiac ACE inhibition, and antioxidant and tissue protective activities. In vitro and in vivo experiments suggest that zofenopril exerts antioxidant properties at clinically achievable tissue concentrations. In endothelial cells, zofenopril enhances nitric oxide production, attenuates atherosclerotic lesion development and inhibits adhesion molecule expression by reducing reactive oxygen species. These peculiar characteristics are reflected in the drug's cardioprotective activity, which has been shown to be greater than that of non-sulphydryl ACE inhibitors. Cardiac hypertrophy was also reduced by chronic zofenopril administration, independently of its blood pressure-reducing effect. ACE inhibitors with a sulphydryl group could have an advantage in improving vascular function and reducing cardiac impairment compared with non-sulphydryl-containing ACE inhibitors. This could explain zofenopril's remarkable clinical efficacy post-infarction, and potentially beneficial use in prevention and therapy of cardiovascular diseases, such as atherosclerosis, thrombosis and heart failure.     

Unnecessary surgery for acute abdomen secondary to angiotensin-converting enzyme inhibitor use

Acute abdominal pain is the reason for 5% to 10% of all emergency department visits. In 1 in every 9 patients, operated on for an acute abdomen, laparotomy is negative. In a minority of patients, the acute abdomen is caused by side effects of medication. We present a case of unnecessary abdominal surgery in a patient with acute abdominal pain caused by intestinal angioedema (AE), which was eventually due to angiotensin-converting enzyme inhibitor (ACE-i) use. We hope that this case report increases awareness of this underdiagnosed side effect. Emergency department physicians, surgeons, internists, and family physicians should always consider ACE-i in the differential diagnosis of unexplained abdominal pain. Since early withdrawal of the medication causing intestinal AE can prevent further complications and, in some cases, needless surgery, we propose an altered version of the known diagnostic algorithm, in which ACE-i and nonsteroidal anti-inflammatory drugs–induced AE is excluded at an early stage.