Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension

OBJECTIVE: To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension. DESIGN AND METHODS: The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12. RESULTS: Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups. CONCLUSIONS: Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.     

Comparison of angiotensin converting enzyme and renin inhibition in rats following myocardial infarction

Renal and systemic hemodynamics were studied in rats 1 month after induction of myocardial infarction by ligation of the left coronary artery. The mean arterial pressure, heart rate, and cardiac index were not different from controls, but there were striking elevations in heart weight (p < 0.001), left ventricular end diastolic pressure (p < 0.002), and renal vascular resistance (p < 0.01). Renal blood flow and the percent of cardiac output perfusing the kidneys were reduced by 18% (p < 0.01) and 14% (p < 0.01), respectively. Acute angiotensin inhibition was studied at a dose of the converting enzyme inhibitor, enalapril, or the renin inhibitor, CP71362, that lowered the mean arterial pressure by 15 mm Hg in normal rats. In normal rats, enalapril and CP71362 were without effect on renal blood flow (RBF), renal vascular resistance (RR), and RBF as a percent of cardiac output. However, in rats with myocardial infarction, enalapril and CP71362 increased the RBF and RBF as a percent of cardiac output and lowered the RR to levels similar to normal controls (p < 0.02). Enalapril and CP71362 were equally effective in reducing the left ventricular end-diastolic pressure and total peripheral resistance in rats with myocardial infarction. These data demonstrate significant intrarenal vasoconstriction following myocardial infarction in the absence of detectable changes in mean arterial pressure or cardiac index. Converting enzyme inhibition or renin inhibition had similar beneficial effects on cardiorenal function, suggesting that both classes of compounds act by a similar mechanism to improve renal hemodynamics in congestive heart failure.     

Serum angiotensin converting enzyme activity in patients with untreated essential arterial hypertension

The serum angiotensin converting enzyme (ACE) in 30 patients with untreated essential arterial hypertension, 30 patients with chronic renal failure accompanied with arterial hypertension and 30 healthy individuals was measured. The subjects of both sexes have been old 35-60 years. The serum ACE activity was determined by the spectrophotometric method, using Hip-Gly-Gly as a substrate. The serum ACE activity significantly increased in patients with arterial hypertension (32.48 +/- 2.02; X +/- SEM) and patients with chronical renal failure accompanied with arterial hypertension (37.10 +/- 1.45) when compared to the healthy individuals (20.83 +/- 1.33). Possible mechanisms of increasing ACE activity with the patients suffering of arterial hypertension are discussed.     

Treatment of essential arterial hypertension with hypercholesterolemia. Effects of an alpha-adrenergic blocker and an inhibitor of the angiotensin converting enzyme

BACKGROUND: Hypertension and hypercholesterolemia are frequently associated with this leading to considerable cardiovascular risk. METHODS: An open parallel randomized study was performed in which the effects of doxazosin, an alpha-adrenergic blocker and enalapril, an inhibitor of the angiotensin converting enzyme were compared in 70 patients with essential high blood pressure and plasma cholesterol levels greater than 240 mg/dl. Following 2-4 weeks of placebo administration the patients were randomly treated with one of the two drugs. When required doses were increased and hydrochlorothiazide added until blood pressure lower than 160/95 mmHg was achieved. After this period the patients were observed for a minimum of 8 weeks. The mean length of the study was of 22 weeks. RESULTS: Both drugs significantly reduced blood pressure without modifying cardiac frequency. Doxazosin tended to favorably modify the lipid profile of the plasma while enalapril significantly reduced the levels of cholesterol, lipids and high density lipoproteins (HDL). Upon termination of the study the total HDL/cholesterol index increased 8.6% in those treated with doxazosin and decreased 5.5% in those receiving enalapril (p < 0.05). CONCLUSIONS: Although doxazosin and enalapril are potent antihypertensive drugs, the effects on plasma lipid obtained with doxazosin indicate that a reduction in cardiovascular risk was achieved with this drug in the patients included in this study.     

The angiotensin converting enzyme inhibitors captopril and enalapril inhibit apomorphine-induced oral stereotypy in the rat

The possible functional interaction between angiotensin and dopamine mechanisms in the rat was investigated by examining the effects of the angiotensin converting enzyme inhibitors captopril and enalapril on apomorphine-induced stereotypy. Apomorphine-induced behaviour was observed, and recorded using a keypad linked to a microcomputer. In agreement with previous findings, low doses of apomorphine induced a syndrome of vacuous mouth movements, penile grooming, yawning and immobility whereas at higher doses the yawning syndrome disappeared to be replaced with sniffing, licking and gnawing. Two antagonism studies were carried out. In the first the effects of captopril on apomorphine-induced behaviour were compared with those of the classical neuroleptic haloperidol, and in the second dose-response curves for the effects of captopril and enalapril on apomorphine-induced behaviour were determined. Captopril had no effect on the apomorphine-induced yawning syndrome whereas this was blocked by haloperidol. In contrast, both captopril and haloperidol blocked oral stereotypy (licking and gnawing) induced by apomorphine but had no effect on sniffing induced by the dopamine agonist. Selective blockade of apomorphine-induced oral stereotypy by angiotensin converting enzyme inhibition was confirmed in the second study in which both captopril and enalapril were observed to antagonize apomorphine-induced gnawing. The inhibition of apomorphine-induced gnawing by enalapril correlated with inhibition of brain angiotensin converting enzyme, but not lung angiotensin converting enzyme, by the drug as assessed by ex vivo penetration studies. These data suggest that angiotensin converting enzyme inhibition modulates the expression of apomorphine-induced oral stereotypy, a response that is thought to be mediated by postsynaptic dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential responses of the heart and vasculature to chronic blood pressure reduction in essential hypertension

In the current study, localization of D-aspartic acid (D-Asp) in rat testis was studied by immunohistochemical and biochemical techniques. Immunohistochemical staining of this tissue using specific polyclonal antibody to D-Asp revealed D-Asp immunoreactivity (IR) in the cytoplasm of germ cells, especially around the region rich in elongate spermatids, the most mature of the germ cells. Weak IR was also noted in cytoplasm of spermatocytes and round spermatids; however, it was negligible in interstitial cells and Sertoli cells. The intensity of immunostaining in each seminiferous tubule differed according to its distinct germ cell composition. In testis of young rats, seminiferous tubules lack elongated spermatids, and D-Asp was found to be localized in spermatocytes, the most mature population of germ cells at that age. We used various toxicants to destroy specific testicular cell populations and to confirm the localization of D-Asp in rat testis. Administration of ethane dimethane sulfonate induced a selective destruction of all Leydig cells in this tissue. This resulted in a significant decrease in the D-Asp level, which was probably due to a drop in testosterone brought about by this treatment, and this was followed by a modulation of spermatogenesis. Three days after treatment with methoxyacetic acid (MAA), many seminiferous tubules were found to lack or to have severe depletions of pachytene spermatocytes, but not of elongate spermatids. This caused reductions in protein content and in the total amount of L-Asp, but not that of D-Asp. Twenty days after treatment with MAA, the depleted population of germ cells progressed through the spermatogenic cycle from pachytene spermatocytes to elongate spermatids. At this time, the level of D-Asp decreased significantly, as did that of L-Asp and protein, consistent with D-Asp localization in elongate spermatids. This decrease in the D-Asp level was also seen with immunostaining.     

Polymorphism of the angiotensin I converting enzyme gene in essential hypertensive patients

In order to study the relationship between plasma and platelet von Willebrand factor (vWF), we used an experimental model of crossed bone marrow transplantation (BMT) between SLA immunocompatible normal and homozygous von Willebrand (vWD) pigs. A normal pig received bone marrow from a vWD pig and a second pig with vWD was engrafted with marrow from a normal pig. Each recipient, after total irradiation of 10 Grays, received by a central catheter 10(10) monocellular bone marrow cells without immunosuppression. The animals were followed for 50 d and no graft rejection or graft-versus-host disease was observed. After aplasia occurring 3 weeks after BMT, white blood cells and platelets returned to normal. Before transplantation, in the vWD pig, vWFAg and vWF activity were not detected in plasma and in platelet and megakaryocyte alpha-granules. After transplantation with normal marrow, platelet vWFAg and platelet vWF activity wer normal and high molecular weight multimers and numerous tubular structures were present in alpha-granules. Before transplantation, the normal pig had normal plasma and platelet vWFAg-vWF activity, normal multimeric pattern, and the platelet and megakaryocyte alpha-granules displayed many tubular structures, eccentrically located in one of their poles, coinciding with immunogold staining vWFAg. After transplantation with homozygous vWD marrow, platelet and megakaryocyte alpha-granules lacked tubular structures. Alpha-granule immunogold staining for vWF was consistently negative, although plasma vWF was at a normal level. In conclusion, this study shows that, unlike other plasma proteins such as fibrinogen. vWF endocytosis does not occur from plasma to the platelet alpha-granules. Platelet and megakaryocyte vWF solely originates from megakaryocyte endogenous synthesis and is independent of plasma vWF.     

Inhibition of angiotensin converting enzyme from sheep tissues by captopril, lisinopril and enalapril

Inhibition of angiotensin converting enzyme(EC 3.4,15.1, ACE) in presence of captopril, lisinopril and enalapril were investigated in kidney, lung and serum of sheep using Hip-His-Leu(HHL) as substrate. The activity in kidney, lung and serum was inhibited at HHL concentration above 5 mM. The inhibitory constants (IC50) ranged between 5.6 nM for serum ACE with lisinopril and 70000 nM for renal ACE with enalapril while Ki ranged from 1.0 nM for serum ACE with lisinopril to 12000 nM for kidney ACE with enalapril. Differences in inhibition observed in different tissues suggest that the inhibitors may block function(s) of ACE to varying degrees in each tissue.     

Blood pressure and renin activity in essential hypertension under pindolol

20 essential hypertension patients with diastolic blood pressure of 100-140 mm Hg were treated with increasing doses (15-45 mg/day by mouth) of pindolol for 14 weeks after an initial placebo period of 5 weeks. Systolic and diastolic blood pressure decreased significantly with as little as 15 mg of pindolol (p less than 0.001). No further changes in systolic and diastolic blood pressure were observed when the doses of pindolol were increased. Plasma renin activity (PRA) determined by radioimmunoassay did not change under increasing doses of pindolol. The blood pressure changes did not correlate with initial PRA or with individual changes in PRA under increasing doses with individual changes in PRA under increasing doses of pindolol. These results do not afford evidence for a renin-dependent hypotensive effect of pindolol.     

Effects of renin inhibition compared to angiotensin converting enzyme inhibition in conscious dogs with pacing-induced heart failure

OBJECTIVE: To compare the effects of angiotensin converting enzyme inhibition (ACEI) (captopril 1 mg/kg i.v.) to direct renin inhibition (CP80794 3 mg/kg i.v.) on left ventricular and systemic hemodynamics and peripheral blood flows in advanced congestive heart failure (CHF). METHODS: Conscious chronically instrumented dogs (n = 14) were treated with captopril, 1 mg/kg, i.v., or CP80794, 3 mg/kg, i.v., before and after development of advanced CHF induced by 4-7 weeks of rapid ventricular pacing. After advanced CHF, comparisons between the inhibitors were made at equihypotensive doses. RESULTS: In advanced CHF, both agents caused comparable reductions in mean arterial pressure (MAP) (-22% from 79 +/- 4 mmHg) and comparable increases (P < 0.01) in cardiac output (CP80794, 1.4 +/- 0.3 to 1.8 +/- 0.1 l/min; captopril, 1.4 +/- 0.1 to 1.9 +/- 0.1 l/min). Neither agent had a significant effect on LV contractility. In contrast, CP80794 caused a greater (P < 0.05) increase in renal blood flow (66 +/- 6% from 64 +/- 5 ml/min) compared to captopril (33 +/- 4% from 66 +/- 7 ml/min). CONCLUSIONS: Renin inhibition with CP80794 and ACEI with captopril caused comparable hemodynamic effects in advanced CHF. However, CP80794 caused significantly greater increases in renal blood flow and suppressed renin activity to a greater degree than captopril.     

The mechanisms of the improvement of insulin sensitivity by angiotensin converting enzyme inhibitor

To investigate the role of kinins in augmentation of insulin sensitivity by angiotensin converting enzyme inhibitor (ACEI), the effects of ACEI (delapril) on the insulin resistance in fructose-fed rats (FFR) were evaluated with or without the administration of bradykinin receptor antagonist (Hoe 140). Male Sprague-Dawley rats were fed on fructose rich chow (FFR) or standard chow (control) for 4 weeks and treated with 10 mg/kg/day of delapril with or without Hoe 140 (0.5 mg/kg/day) for an additional 2 weeks. Steady state plasma glucose (SSPG) and steady state plasma insulin (SSPI) were determined while the rats were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. Mean blood pressure (MBP), SSPG and SSPI were significantly higher in FFR than in control, and were significantly lower in the FFR+delapril than in FFR+vehicle. There were no difference in MBP, SSPG and SSPI between FFR+delapril+vehicle and FFR+delapril+Hoe 140. We concluded that the main mechanisms of improving the insulin sensitivity by ACEI may not be the enhancement of kinins but the suppression of angiotensin II in FFR.     

The significance of converting enzyme inhibitor angiotensin I to angiotensin II in treatment of patients with coronary disease]

Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the treatment of hypertension and heart failure. The renin-angiotensin-aldosterone system is complex and acts as a circulating hormonal system, a local endogenous tissue system and neuromodular. Current experimental evidence suggests that ACE inhibitors reduce the risk associated with atherosclerotic cardiovascular disease. The antiatherogenic action of ACE inhibitors is related to complex effects mediated by these agent, including an antiproliferative and antimitotic action, beneficial effects on endothelial function, plaque-stabilizing effects and the action of these agents on the sympathetic nervous system. The role of ACE inhibitors in preventing the clinical sequale of atherosclerotic cardiac disease has been evaluated in various patient populations. Several small trial assess the effects of ACE inhibitors in severity of angina pectoris have reported conflicting results, with benefit is some patients and no benefit or even exacerbation of angina in others, indicating that ACE inhibitors do not have consistent antianginal effects in short-term study. ACE inhibitors have the theoretical potential to prevent restenosis after PTCA but they do not prevent restenosis and has no effect on overall clinical outcome. New data suggest that ACE inhibitors may be effective therapy fir patients following acute myocardial infarction. The renin-angiotensin system, is activated during new myocardial infarction and has an impact on the process of remodeling of the left ventricle which causes ist dysfunction and heart failure. In most of the large mortality trials the rationale for early treatment with ACE inhibitors after myocardial infarction was stated. ACE inhibitors have a positive effect in preventing the ventricular dilatation and they reduce the rate of reinfarctions and the mortality rate.     

The effect of minoxidil on blood pressure and plasma renin activity in patients with essential and renal hypertension

The effect of the new vasodilator, minoxidil, on blood pressure and plasma renin activity was studied in 21 hypertensive patients: 12 patients with essential and 9 with renal hypertension. The average maximum dosage of minoxidil was 27.9 +/- 6.0 mg/day (M +/- SD). Average duration of treatment was 84.5 days. During the observation period the average systolic blood pressure fell from 195 +/- 18 to 159 +/- 7 mm Hg (M +/- SD), and the mean diastolic blood pressure fell from 120 +/- 8.3 to 92.5 +/- 8 mm Hg (p less than 0.01). These patients had been treated earlier with other antihypertensive agents, such as reserpine, saluretics, hydralazine, alpha-methyldopa, and clonidine, without any significant reduction in blood pressure. Before treatment, plasma renin activity after resting was 59 +/- 6.4 ng/ml/16 h (M +/- SE) and after saluretics and orthostasis 89 +/- 12.7 ng/ml/16 h. After treatment, the decline in renin value after resting was statistically significant: 42.7 +/- 3.3 ng/ml/16 h (p less than 0.05), and the stimulated renin had fallen to 70 +/- 3.4 ng/ml/16 h (p greater than 0.1). A comparison of the renin stimulation values of patients with renal hypertension also revealed a significant reduction (p less than 0.01). Side effects which appeared at a daily dose of 15 to 30 mg consisted mainly of tachycardia and fluid retention and could be controlled by the administration of propranolol and chlorthalidone. In 5 women and in 1 man was observed a cosmetically disturbing, reversible hypertrichosis. Orthostatic hypotension was observed in one patient. Minoxidil is an effective antihypertensive agent. However, because of its side effects, it generally must be administered with beta-receptor blocking agents and saluretics. It is possible that its blood pressure lowering effect is due, at least in part, to a suppression of the plasma renin activity.     

Tissue availability of insulin-like growth factor I is inversely related to insulin resistance in essential hypertension: effects of angiotensin converting enzyme inhibition

The effects of adrenoceptor agonists on the transepithelial Cl- conductance (GCl) in the skin of several amphibian species, both toads and frogs, were studied. Epinephrine (Epi) from the serosal side selectively and reversibly inhibited the voltage-activated GCl in toad skin and the short-circuit GCl in frog skin. The main effects of activation of the adrenoceptors must reside in the skin epithelium and not in the glands, since measurements were made both from intact skins and split epithelia with essentially the same results. Effective concentrations of Epi were variable among individual tissues. GCl was reduced to 34+/-17% (n=46) with 1 micromol/l Epi, but in some tissues 0.1 micromol/l inhibited more than 80% of GCl, whereas some preparations were little influenced at >3 micromol/l Epi. The affected receptor type was identified by the use of the alpha1-agonist phenylephrine, which mimicked the response of Epi at concentrations above 30 micromol/l, whereas the alpha2-agonists xylazine and iodoclonidine had no effect at supramaximal concentrations. Prazosin, a specific alpha1-antagonist, reduced or eliminated the inhibition by Epi, but the response pattern suggests a low affinity. The alpha2-antagonist yohimbine, at concentrations 100 micromol/l CPT-cAMP). Preincubation of the serosal medium with Ca2+-free solution (in the presence of 2 mmol/l EGTA) for extended periods of time (>30 min) eliminated the response to Epi. It is concluded that alpha1-adrenoceptors participate in the physiological control of voltage-activated Cl- conductance in amphibian skin epithelium via modulation of intracellular Ca2+, presumably by efflux from intracellular stores.     

Compartmentalization and cyclic variation of immunoreactivity of renin and angiotensin converting enzyme in human endometrium throughout the menstrual cycle

Renin and angiotensin converting enzymes (ACE) are responsible for the generation of angiotensin II which regulates blood pressure and fluid/electrolyte homeostasis. The cellular localization and cyclic distribution of renin and ACE in human endometrium are demonstrated in this study. Immunohistochemical studies revealed that both renin and ACE were consistently localized in the endometrial glandular epithelia throughout the menstrual cycle; however, the immunostainings respectively for ACE and renin were weak and moderate in stromal cells of proliferative endometrium and negligible in secretory endometrium. No renin immunostaining was detected around endometrial blood vessels. Although endothelial cells consistently stained for ACE, no renin immunoreactivity was detected in these cells during the menstrual cycle. Western blot analysis using ACE antibody directed against human kidney identified a single protein band with a relative molecular mass of approximately 153 kDa. The intensity of this band showed cyclic variation during the menstrual cycle with the highest ACE expression during the late secretory phase and at menses suggesting that ACE plays a role in the initiation of menstruation. The differences in the cellular distribution patterns of these two enzymes further supports our previous proposition that angiotensin II has different functions at the different stages of the menstrual cycle.     

Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and nephroangiosclerosis

An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene significantly influences circulating ACE levels and plays a role in the development of target organ damage, that is, left ventricular hypertrophy in essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have examined the role of the I/D polymorphism in essential hypertensive patients with renal involvement. The study was divided in two independent protocols. In protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential hypertensive patients with a clinical and histopathological diagnosis of nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria and renal hemodynamic parameters were investigated in 75 patients with EH with normal renal function and a strong family history of hypertension. As control group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of cardiovascular diseases were studied. The ACE variants were determined by PCR and the genotypes were classified as DD, DI and II. In protocol 1, patients with nephroangiosclerosis displayed a significant difference in the genotype distribution (57% DD, 27% DI, 16% II) when compared to the control population (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in genotype distribution between hypertensive patients with normal renal function (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no differences in age, blood pressure, microalbuminuria and duration of the disease among the three genotypes in the EH group from protocol 2. Taken together, these findings suggest that the DD genotype of ACE is associated with histopathologic-proven kidney involvement in patients with EH and that this polymorphism could be a potential genetic marker in hypertensives at risk of renal complications.     

Synergistic effects of combined converting enzyme inhibition and angiotensin II antagonism on blood pressure in conscious telemetered spontaneously hypertensive rats

OBJECTIVE: To investigate the chronic effects of combined administration of an angiotensin II receptor antagonist (valsartan) and an angiotensin converting enzyme inhibitor (benazeprilat) on blood pressure and heart rate in conscious telemetered spontaneously hypertensive rats. METHODS: Blood pressure and heart rate were monitored (by radiotelemetry) during 2-week infusions of 0.5-10 mg/kg valsartan per day and 0.5-10 mg/kg benazeprilat per day, alone or in combination, into conscious spontaneously hypertensive rats. Also, responses of blood pressure in conscious spontaneously hypertensive rats to exogenous angiotensin I and II were determined. RESULTS: Synergistic antihypertensive effects were observed when valsartan and benazeprilat were coadministered at submaximal monotherapy doses in the range 0.5-1.5 mg/kg per day. For all combination groups, the area over the curve (mmHg x days) for lowering of blood pressure was significantly greater (synergy) than that predicted from the sum of the monotherapy responses. Combination therapy abrogated pressor responses to angiotensin I more effectively than did comparable doses of the monotherapies. CONCLUSIONS: These results demonstrate that combination therapy aimed at interrupting operation of the renin-angiotensin system simultaneously at multiple sites can prevent the partial escape which occurs during chronic angiotensin converting enzyme inhibitor monotherapy. Furthermore, multiple-site intervention results in a more efficacious antihypertensive response than that achieved with high doses of the individual monotherapies.     

Effect of the angiotensin converting enzyme inhibitor, captopril, on proteinuria in chronic glomerular disease

The antiproteinuric effect of the angiotensin-I-converting enzyme inhibitor, captopril, was studied in 14 patients (10 men and 4 women, age range of 24 to 60 years) with chronic glomerulonephritis in whom IgA nephritis had been confirmed by renal biopsy. Eight of the 14 patients had received antihypertensive drugs such as calcium channel blockers, diuretics or beta-blockers. Captopril was added to these regimens at 25 mg twice daily in 3 patients, and 37.5 mg in 11 patients. Proteinuria decreased from 2.55 +/- 0.48 g/day to 1.58 +/- 0.35 g/day within three months after the start of administration. In 4 patients (28.6%), the extent of reduction was over 50%, and in 8 patients (57.1%), over 25%. Blood pressure, creatinine clearance and serum creatinine were not changed significantly. There was a positive linear correlation between the extent of reduction of proteinuria and the increase in plasma renin activity (r = 0.93, p < 0.001). We conclude that captopril reduces proteinuria in some patients with IgA nephritis whose plasma renin activity responds to the drug.     

The influence of temocapril, an angiotensin converting enzyme inhibitor, on the cyclosporine-induced nephrotoxicity

PURPOSE: We examined the effect of temocapril (Tem), an angiotensin converting enzyme inhibitor (ACEI), on the cyclosporine-induced nephrotoxicity (CsA-NT) in rats. MATERIALS AND METHODS: Male Wistar rats were used. Group 1 (G1) received a medium (i.e. olive oil) only, group 2 (G2) received CsA (30 mg./kg./d) only, group 3 (G3) received both CsA (30 mg./kg./d) and Tem (80 micrograms./kg./d), and group 4 (G4) received Tem (80 micrograms./kg./d) only. Each group consisted of 5 animals. Drugs were given orally for fourteen days. Then, renal cortical blood flow (RCBF) and concentrations of serum creatinine (S-Cr), serum potassium (S-K), whole blood CsA (WB-CsA), serum aldosterone (Ald), and plasma renin activity (PRA) were measured. The creatinine clearance (CCr) was also calculated. Kidneys were processed to the light microscopic examination with Bowie stain, and the size of the renin granules (S-RGs) was estimated by an image analysis system. RESULTS: G2 showed a decrease of RCBF (p < 0.01), an increase of S-Cr (p < 0.01), a decrease of CCr (p < 0.01), an increase of S-K (p < 0.05), and an increase of S-RGs (p < 0.01). Compared with G2, G3 showed significant improvement in RCBF (p < 0.01) and S-Cr (p < 0.05), but still showed significant impairments in all indices (p < 0.01 or p < 0.05, vs control). G4 showed no remarkable changes comparing with G1, except a significant (p < 0.01, vs. control) increase of S-K. G3 showed additional effect on the increase of S-K (p < 0.01, vs. control and G2). Tem showed no significant influence on the WB-CsA level. The serum Ald and PRA levels were not significantly changed by these drugs. CONCLUSIONS: These data are compatible with the hypothesis that the vasoconstriction of the afferent arterioles (AAs) is a principal mechanism of CsA-NT. The increase of RGs may be the result of both increased production and inhibited secretion of renin.