enalapril and zofenopril

The pathogenic role of angiotensin-converting enzyme (ACE) inhibition in hypertensive patients regarding endothelial progenitor-cell (EPC) function is still poorly understood. The aim of the study was to evaluate EPC number, function, and relationship to carotid intima media thickness (IMT) progression.. We studied 36 newly diagnosed mildly hypertensive patients free of cardiovascular disease and related risk factors without prior or concurrent therapy with ACE inhibitors. Patients were randomized to receive enalapril 20 mg/day (n = 18) or zofenopril 30 mg/day (n = 18). EPC number and migrating capacity, plasma nitrite and nitrate (NOx), and isoprostane concentrations were evaluated. Carotid IMT was determined by ultrasonography at baseline and after 1 and 5 years of follow-up.. EPC number increased during the follow-up, with no statistical differences between treatment groups. There was an inverse correlation between circulating EPCs and IMT increase over time. Plasma NOx decreased during the study without evident differences between treatment groups. Isoprostanes decreased more markedly in zofenopril-treated patients. Multiple linear regression model demonstrated that carotid IMT was significantly inversely correlated with EPC but not with migratory cells after adjusting for confounders.. The study demonstrated that EPC levels increased during the follow-up in both groups of newly diagnosed hypertensive patients treated with ACE inhibitors. These drugs prevented progression of vascular damage, with an inverse correlation between circulating EPC levels and IMT values.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Captopril; Carotid Arteries; Cell Count; Cell Movement; Cells, Cultured; Enalapril; Endothelial Cells; Follow-Up Studies; Humans; Hypertension; Isoprostanes; Middle Aged; Nitrates; Nitrites; Regression Analysis; Stem Cells; Treatment Outcome; Tunica Intima; Ultrasonography

Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors exert antiatherosclerotic effects in preclinical models and antioxidant effects in patients. However, whether ACE inhibitors have any clinically significant antiatherogenic effects remains still debated.. In mildly hypertensive patients, we evaluated the effect of the sulfhydryl ACE inhibitor zofenopril in comparison with the carboxylic ACE inhibitor enalapril on carotid atherosclerosis (intima-media thickness [IMT] and vascular lumen diameter) and systemic oxidative stress (nitrite/nitrate, asymmetrical dimethyl-l-arginine, and isoprostanes).. In 2001, we started a small prospective randomized clinical trial on 48 newly diagnosed mildly hypertensive patients with no additional risk factors for atherosclerosis (eg, hyperlipidemia, smoke habit, familiar history of atherosclerosis-related diseases or diabetes). Patients were randomly assigned either to the enalapril (20 mg/d, n = 24) or the zofenopril group (30 mg/d, n = 24); the planned duration of the trial was 5 years. Carotid IMT and vascular lumen diameter were determined by ultrasonography for all patients at baseline and at 1, 3, and 5 years. Furthermore, nitrite/nitrate, asymmetrical dimethyl-l-arginine, and isoprostane levels were measured.. In our conditions, IMT of the right and left common carotid arteries was similar at baseline in both groups (P = NS). Intima-media thickness measurements until 5 years revealed a significant reduction in the zofenopril group but not in the enalapril group (P < .05 vs enalapril-treated group). This effect was coupled with a favorable nitric oxide/oxidative stress profile in the zofenopril group.. Long-term treatment with the sulfhydryl ACE inhibitor zofenopril besides its blood pressure-lowering effects may slow the progression of IMT of the carotid artery in newly diagnosed mildly hypertensive patients.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Captopril; Carotid Arteries; Carotid Stenosis; Dinoprost; Enalapril; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Tunica Intima; Tunica Media; Ultrasonography

Angiotensin-converting enzyme inhibitors (ACEIs) are used in the management of a range of cardiovascular disorders and are well established in primary as well as secondary cardiovascular prevention programmes. Over the years, several second- and third-generation ACEIs have been introduced into the clinic. In a comparative study in patients with mild to moderate hypertension, the efficacy and safety of zofenopril 30 mg od (with an up-titration to 60 mg od after 4 weeks in non-responder patients) was compared with enalapril 20 mg od (with an up-titration to 40 mg od after 4 weeks in nonresponders) during 12 weeks of treatment. Both treatments significantly reduced systolic (SBP) and diastolic blood pressure (DBP). BP reduction was significantly greater with zofenopril (30 mg/day) during the initial 4 weeks of treatment compared with enalapril (20 mg/day). A larger proportion of patients needed dose up-titration with enalapril compared with zofenopril to reach preset BP goals. After 12 weeks of treatment and after appropriate dose up-titration, SBP and DBPs were lowered to similar extent in the two treatment groups, resulting in no differences between the groups in terms of response and control rates. A similar number of patients reported adverse events in the two study groups. However, the severity of adverse events were significantly milder with zofenopril compared with enalapril. In mild to moderate hypertensive patients, zofenopril treatment results in a more pronounced lowering of BP compared with enalapril at recommended dose levels. Additionally, at clinical and comparative antihypertensive doses, zofenopril presents a more beneficial adverse event profile compared with enalapril.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Dose-Response Relationship, Drug; Double-Blind Method; Enalapril; Female; Humans; Hypertension; Male; Middle Aged

Essential hypertension is associated with enhanced LDL oxidation and impaired endothelium-dependent vasodilation. The antioxidant status is linked to the nitric oxide (NO) pathway. Sulfhydryl angiotensin-converting enzyme (ACE) inhibitors inhibit oxidative stress and atherogenesis in experimental models; therefore we tested whether this beneficial antioxidant activity could be also clinically relevant in patients with essential hypertension.. Plasma LDL oxidizability was investigated initially in untreated normocholesterolemic patients with moderate essential hypertension without clinically evident target organ damage (n = 96) and in control normotensive subjects (n = 46). Patients were then randomly assigned into two age- and sex-matched groups to receive the new sulfhydryl ACE inhibitor zofenopril (15 to 30 mg/d; n = 48) or enalapril (20 mg/d, n = 48). LDL oxidizability was evaluated (generation of malondialdehyde, MDA) and systemic oxidative stress was evaluated by isoprostanes (8-isoPGF2alpha). Asymmetrical dimethyl-L-arginine (ADMA), a competitive inhibitor of endothelial NO synthase, and plasma nitrite and nitrates (NOx) were also measured.. LDL from hypertensive subjects had enhanced susceptibility to oxidation in vitro compared with that in control subjects (P <.05). Similarly, isoprostanes were significantly increased (P <.01) in hypertensive subjects versus control subjects. After 12-week treatment, MDA levels were significantly reduced by zofenopril (P <.05) but not enalapril treatment (P = not significant). Isoprostanes were normalized after zofenopril treatment (P <.03), whereas enalapril was ineffective. After treatment with both ACE inhibitors, plasma NOx concentrations were significantly reduced (P <.05). Similarly, hypertension increased ADMA concentration compared with the normotensive state, whereas ACE inihibition elicited a significant decrease. However, the reduction of ADMA concentration was significantly higher in patients receiving sulfhydryl ACE inhibition (P <.05 vs enalapril).. The sulfhydryl ACE inhibitor zofenopril reduces oxidative stress and improves the NO pathway in patients with essential hypertension. If confirmed in a large multicenter clinical trial, our data suggest a possible vasculoprotective effect of the compound in retarding vascular dysfunction and atherogenesis that often develops rapidly in hypertensive patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arginine; Captopril; Enalapril; Female; Humans; Hypertension; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress

Zofenopril calcium (CAS 81938-43-4) is a new angiotensin converting enzyme (ACE) inhibitor, which in addition to the typical activity of the class, proved to possess a specific cardioprotective effect due also to the presence of the sulfhydryl group. In this trial zofenopril calcium and enalapril maleate (CAS 76095-16-4) were given to 20 healthy volunteers of both sexes in repeated dose regiment at two dose levels: 30 mg and 60 mg zofenopril calcium and 10 mg and 20 mg enalapril maleate. The study was conducted according to a two-period, two-sequence, crossover design, with washout. ACE activity in serum and zofenopril, zofenoprilat, enalapril and enalaprilat plasma concentrations were determined during and on the last day of the two study periods. Both zofenopril and enalapril were extensively converted through hydrolysis to their active metabolites zofenoprilat and enalaprilat, respectively. Zofenopril exhibited a complete and a more rapid hydrolysis rate compared to enalapril, which is reflected by the higher metabolite to parent drug ratio of Cmax and AUCss, tau showed by this compound. Even though only two dose levels were investigated in this trial, the pharmacokinetics of both drugs seem to be linear. In line with previous trials, both compounds at both dose levels investigated produced complete or almost complete inhibition of ACE activity in serum, for a period lasting 6-8 h after administration, the inhibition being still relevant 24 h thereafter. The tolerability of the two drugs at both dose levels proved to be very good as demonstrated by subjective and objective symptoms, by the absence of relevant adverse events, and by laboratory biochemical parameters and vital signs evaluated before and after the trial. Blood pressure showed a fairly decreasing trend with both the drugs, systolic and diastolic blood pressure values being however within normal range in all the subjects. In no case symptoms of hypotension were experienced. In conclusion, zofenopril calcium and enalapril maleate show very good tolerability and appear to exert similar activity on serum ACE. The main difference in the pharmacokinetics of the two compounds is the conversion from pro-drug to the active metabolite which is faster with zofenopril.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Area Under Curve; Biotransformation; Blood Pressure; Captopril; Chromatography, High Pressure Liquid; Enalapril; Female; Heart Rate; Humans; Male; Peptidyl-Dipeptidase A

The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anticonvulsants; Captopril; Drug Synergism; Enalapril; Female; Fosinopril; Male; Mice; Motor Activity; Seizures

The aim of this study is to compare possible protective effects of zofenopril, enalapril and valsartan against both ischaemia/reperfusion injury as well as acute doxorubicin cardiotoxicity. All three agents have never been compared in this setting before.. Sixty-four male rats were divided into eight groups by computer-generated random numbers and each group included 8 rats. Groups 1, 2, 3 and 4, respectively, received 0.5 ml distilled water, 15 mg/kg/day zofenopril, 2 mg/kg/day enalapril, and 30 mg/kg/day valsartan intragastrically for 7 days. Groups 5, 6, 7, and 8 underwent the same procedures as groups 1, 2, 3 and 4. On the 7th day, groups 1-4 and groups 5-8, respectively, were injected with serum saline or 20 mg/kg doxorubicin intraperitoneally. On the 9th day, isolated rat hearts were perfused in the Langendorff perfusion system. At the end of each Langendorff experiment, the rat hearts were kept for histological analysis. Left ventricular systolic pressures were negatively affected by doxorubicin with ischaemia (group 5 initially: 61.4 +/- 13.6 mmHg--post-ischaemic (PI): 20.7 +/- 17.5 mmHg (P = 0.0002), group 6 initially: 63 +/- 18.2 mmHg--PI: 24.2 +/- 24.3 mmHg (P = 0.0135), group 7:82 +/- 26 mmHg--PI: 14.3 +/- 12.1 mmHg (P < 0.0001), group 8:73.1 +/- 27.8 mmHg--PI: 20.4 +/- 27.3 mmHg (P < 0.0001). The lowest troponin I levels (group 2: 0.3 +/- 0.2 ng/ml, group 6:0.2 +/- 0.1 ng/ml (P = 0.003) versus the groups' baseline value) were recorded in the groups of zofenopril in the coronary perfusate during post-ischaemic period. Light microscopic evaluation revealed marked cardiac damage with doxorubicin, since zofenopril treatment prevented a doxorubicin induced increase in the histopathological scores.. In respect of our results zofenopril could be considered more effective than enalapril and valsartan in protecting against both ischaemia/reperfusion injury as well as doxorubicin induced-cardiotoxicity.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Doxorubicin; Enalapril; Heart Diseases; Hemodynamics; Humans; Male; Rats; Rats, Wistar; Reperfusion Injury; Tetrazoles; Valine; Valsartan

The present study investigates the effects of chronic administration of ACEIs (angiotensin-converting-enzyme inhibitors; either zofenopril or enalapril) in combination with a diruetic (hydrochlorothiazide) on BP (blood pressure) increase and renal injury induced by L-NAME (NG-nitro-L-arginine methyl ester), an inhibitor of NO (nitric oxide) synthesis. Rats were untreated or received L-NAME alone, L-NAME+zofenopril+hydrochlorothiazide or L-NAME+enalapril+hydrochlorothiazide for 8 weeks. L-NAME treatment resulted in marked elevation in BP and mortality. Treatment with either ACEI and diuretic prevented the increase in BP induced by L-NAME, reduced the death rate and improved excretory parameters. Renal injury in the L-NAME group was severe, but, in the groups treated with either ACEI and diuretic, glomerular and tubulointerstitial lesions were not observed and the intensity, number and size of vessels affected was reduced. However, the efficacy of zofenopril+diuretic was superior to that of enalapril+diuretic in reducing vascular alterations. Oxidative stress indices and the expression of NO synthase and nitrotyrosine were normalized by the treatments. In conclusion, the combined treatment of zofenopril or enalapril with hydrochlorothiazide completely prevented the development of arterial hypertension induced by L-NAME. Renal morphological and functional alterations in the hypertensive animals were also almost completely normalized, but the treatment with zofenopril+diuretic produced a more complete organ protection. The protective effect is related to an activation of endothelial NO synthase expression and to a normalization of the oxidative stress parameters due to the inhibition of angiotensin II.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Diuretics; Drug Therapy, Combination; Enalapril; Hydrochlorothiazide; Hypertension; Kidney; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Rats; Rats, Sprague-Dawley; Tyrosine

The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE(-/-)) mice. Groups of 2-month-old male mice received either placebo (N=10), 0.05 mg/kg/day of zofenopril (N=10), 1 mg/kg/day of zofenopril (N=10), 5 mg/kg/day of captopril (N=10) or 0.5 mg/kg/day of enalapril (N=8). After 29 weeks of treatment, computer-assisted imaging analysis revealed that zofenopril reduced the aortic cumulative lesion area by 78% at 0.05 mg/kg/day and by 89% at 1 mg/ml/day of zofenopril compared to that of the placebo (P<0.0001). Captopril reduced by 52% aortic lesions compared to placebo (P<0.01 vs. placebo; P<0.05 vs. zofenopril at both doses). Enalapril did not reduce aortic lesions. Furthermore, 0.05 mg/kg/day of zofenopril reduced susceptibility of plasma LDL to in vitro oxidation compared to captopril, enalapril or placebo, as shown by significant reduction of malondialdehyde content (P<0.001 vs. placebo or enalapril; P<0.05 vs. captopril), as well as by the prolongation of lag-time (P<0.01 vs. placebo or enalapril P<0.05 vs. captopril). More importantly, mice treated with 1 mg/ml/day of zofenopril had a significant decrease in the intimal immunohistochemical presence of oxidation-specific epitopes on oxLDL (NA59 monoclonal antibody, P<0.01), macrophages derived foam cells (F4/80 monoclonal antibody, P<0.05) and native LDL (NP monoclonal antibody, P<0.01) compared to placebo, captopril or enalapril. Thus, chronic treatment with the new sulfhydryl ACE-inhibitor zofenopril has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic apoE(-/-) mice. This protection was significantly higher than that reached with captopril and at lower doses of the drug. Treatment with 0.5 mg/kg/day of enalapril did not provide any protective effect.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Aortic Valve Stenosis; Apolipoproteins E; Arteries; Arteriosclerosis; Blood Pressure; Captopril; Cholesterol; Disease Models, Animal; Dose-Response Relationship, Drug; Enalapril; Epitopes; Immunohistochemistry; Lipid Peroxidation; Lipoproteins, LDL; Male; Mice; Mice, Knockout; Oxidation-Reduction; Oxidative Stress; Peptidyl-Dipeptidase A; Random Allocation; Sulfhydryl Reagents; Time Factors; Treatment Outcome

To examine the inhibitory potential of enalapril [and other angiotensin converting enzyme (ACE) inhibitors] on glycylsarcosine (GlySar) transport by the high-affinity renal peptide transporter.. Studies were performed in rabbit renal brush border membrane vesicles in which the uptake of radiolabeled GlySar was examined in the absence and presence of captopril, enalapril, enalaprilat, fosinopril, lisinopril, quinapril, quinaprilat, ramipril and zofenopril.. Kinetic analyses demonstrated that enalapril inhibited the uptake of GlySar in a competitive manner (Ki approximately 6 mM). Fosinopril and zofenopril had the greatest inhibitory potency (IC50 values of 55 and 81 microM, respectively) while the other ACE inhibitors exhibited low-affinity interactions with the renal peptide transporter. With respect to structure-function, ACE inhibitor affinity was strongly correlated with drug lipophilicity (r = 0.944, p < 0.001 for all ACE inhibitors; r = 0.983, p < 0.001 without enalaprilat, quinaprilat and quinapril).. The data suggest that enalapril and GlySar compete for the same substrate-binding site on the high-affinity peptide transporter in kidney, and that ACE inhibitors can interact with the renal carrier and inhibit dipeptide transport.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Binding, Competitive; Captopril; Carrier Proteins; Cell Membrane; Dipeptides; Dose-Response Relationship, Drug; Enalapril; Fosinopril; Isoquinolines; Kidney; Kinetics; Lipid Metabolism; Lipids; Lisinopril; Male; Microvilli; Peptide Transporter 1; Quinapril; Rabbits; Ramipril; Symporters; Tetrahydroisoquinolines

Angiotensin converting enzyme inhibition in heart, kidney, and serum were studied ex vivo after oral administration of lisinopril (10 mg/kg), zofenopril (10 mg/kg), and captopril (30 mg/kg) to rats to study the time course, degree, and sites of inhibition of ACE by a quantitative in vitro autoradiography and enzymatic assay. ACE activity in all regions of the heart, kidney, and serum was markedly reduced 4 h after administration of lisinopril and zofenopril and only partially recovered toward control levels at 24 h. After captopril treatment, ACE activity was partially inhibited in heart, kidney, and serum at 1 h and fully recovered toward control levels in most regions at 24 h. These results suggest that these inhibitors reduce ACE in all regions of the heart and kidney without regional selective inhibition. Lisinopril and zofenopril at these doses produced longer-lasting ACE inhibition than captopril. ACE recovery after ACE inhibitor treatment in serum was faster than in heart or kidney.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Autoradiography; Captopril; Enalapril; Iodine Radioisotopes; Kidney; Lisinopril; Male; Myocardium; Oxidation-Reduction; Peptidyl-Dipeptidase A; Rats; Rats, Inbred Strains

The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction. Spirapril contains no sulphydryl group, whereas zofenopril is a sulphydryl containing ACE inhibitor.. Experimental myocardial infarction was induced by ligation of the left coronary artery. Sham operated animals served as controls. Treatment with spirapril (2-2.5 mg.kg-1.d-1) or zofenopril (12-15 mg.kg-1.d-1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks. After the treatment period, all rats were killed. The heart was rapidly removed and perfused as described by Langendorff. Heart rate and left ventricular pressure were measured both at baseline and during stimulation with isoprenaline (6 nM). Heart and lung weights were determined.. Normotensive male Wistar rats (220-240 g) were used.. Experimental myocardial infarction considerably increased left ventricular cavity volume. Chronic treatment with either spirapril or zofenopril significantly attenuated this increase in volume. In infarcted rats, the increase in total heart and lung weight was also significantly reduced by chronic treatment with spirapril and zofenopril, indicating that these compounds reduce cardiac mass and pulmonary congestion in congestive heart failure due to myocardial infarction. There were no significant differences between treatment with spirapril and zofenopril. In the isolated and perfused rat heart, myocardial infarction significantly decreased both heart rate and left ventricular pressure. Converting enzyme inhibition only affected heart rate. Heart rate was significantly higher in infarcted animals treated with spirapril and zofenopril than in untreated infarcted animals.. Both spirapril and zofenopril attenuated ventricular enlargement and cardiac hypertrophy in rats with congestive heart failure after myocardial infarction when treatment was started in the acute phase of myocardial infarction. No additional role could be attributed to the sulphydryl moiety of zofenopril. It is also suggested that these two ACE inhibitors modify cardiac sympathetic activity in rats with congestive heart failure, but more studies are needed to confirm these findings.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Disease Models, Animal; Enalapril; Heart; Heart Rate; Isoproterenol; Male; Myocardial Infarction; Myocardium; Rats; Rats, Inbred Strains

1. Seven drugs (captopril, zofenopril, enalapril, ramipril, lisinopril, fosinopril, and SQ 29,852) were compared in vitro in homogenates of aorta, brain, heart, lung, and kidney and in sera of spontaneously hypertensive rats (SHR) both with respect to potencies of their active moieties as inhibitors of angiotensin-converting enzyme (ACE), and, where applicable, rates of hydrolysis of their prodrug ester functions. 2. In ex vivo dose-response and time-course studies, the inhibitory effects of the seven drugs on tissue ACEs and their relative distributions to SHR tissues were compared following oral administration. 3. The relative potencies of the inhibitory moieties of the drugs (in parentheses) and the normalized 'equiactive' oral doses employed for time-course studies were: SQ 29,852 (1.0), 100 mg kg-1; captopril (3.5), 30 mg kg-1; enalapril (12), 20 mg kg-1; fosinopril (13), 25 mg kg-1; zofenopril (20), 10 mg kg-1; lisinopril (24), 10 mg kg-1; and ramipril (51), 5 mg kg-1. 4. Following oral administration of the drugs to SHR, the degree and duration of ACE inhibition in aorta and lung correlated with the antihypertensive actions, with ramipril, lisinopril, and zofenopril producing effects of the greatest magnitude and duration. 5. Ramipril and enalapril did not inhibit brain ACE ex vivo; captopril and zofenopril had modest but short-lasting effects; and fosinopril, lisinopril, and SQ 29,852 had long-lasting inhibitory actions, which, with the latter two, were delayed in onset. 6. All of the drugs produced significant inhibition of kidney ACE, with ramipril and fosinopril having somewhat weaker effects, perhaps due to biliary routes of excretion. 7. Captopril, fosinopril, and particularly zofenopril inhibited cardiac ACE ex vivo with degrees and durations that were marked compared with those of the other drugs; preliminary studies with isolated hearts suggest a possible relationship between inhibition of cardiac ACE and preservation of cardiac function subsequent to ischaemia.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Animals; Bridged Bicyclo Compounds; Captopril; Chemotherapy, Cancer, Regional Perfusion; Dose-Response Relationship, Drug; Enalapril; Fosinopril; Heart; Hypertension; Lisinopril; Male; Organophosphorus Compounds; Proline; Ramipril; Rats; Time Factors; Tissue Distribution