Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lisinopril (L), a novel angiotensin converting enzyme inhibitor, was studied as sole drug in the management of hypertensive, dialysis-treated, end-stage renal failure patients to assess its efficiency, tolerance, and removal by dialysis. High blood pressure (BP) was defined as sitting diastolic (D) BP greater than or equal to 95 mm Hg. Ten patients, two females and eight males, were treated for 12 weeks. Their features were age 49 +/- 14 years; dialysis duration 43 +/- 25 months; body weight 61 +/- 10 kg; and body mass index 21.7 +/- 3 (mean +/- SD). Serum L concentrations were measured regularly by radioimmunoassay, both before and after dialysis, which was performed with Cuprophane membranes three times per week. L, 2.5 mg orally, was given every 24 h initially; in six patients, dosage was decreased to an alternate or once-a-week schedule, because of a hypotensive effect during dialysis. At 12 weeks, BP--as compared to prestudy BP--was decreased in eight of nine patients (one patient had been withdrawn after kidney transplantation), and not changed in one patient (mean +/- SD): sitting DBP from 107 +/- 7 to 87 +/- 10 mm Hg, p less than 0.001; erect DBP from 105 +/- 5 to 86 +/- 10 mm Hg, p less than 0.001. L serum concentration was decreased by dialysis, the mean ratio of post-/predialysis serum L concentrations was 0.47 +/- 0.07 (n = 67). No side effects were disclosed, except for three patients, in whom hemoglobin decreased, while two of them also received quinine for a febrile illness of viral origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of hypertension with lisinopril in end-stage renal failure. 248 55

One-hundred patients suffering from slight-moderate hypertension (53 m, 47 f, aged between 18 and 78, average 49.08) have been studied in order to assess the effectiveness and tolerance of lisinopril ("Zestril", ICI-Pharma), a new ACE inhibitor in a single daily administration at doses of between 10 and 80 mg in relation to pressure values. Monotherapy with Lisinopril proved effective in 84 patients (88.4%), in 74 of whom (7.9%) pressure values were returned to normal. 11 patients (11.6%) did not respond to treatment. In most cases, the result was obtained with a dose of 20 mg in a single administration (32.6%). The incidence of side-effects was limited and in no case required the withdrawal of the drug.
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PMID:[Multicenter clinical study of the antihypertensive activity of lisinopril]. 253 7

To determine whether acute effects of the angiotensin converting enzyme inhibitor lisinopril are maintained during long-term therapy, 19 patients were studied using right-sided heart catheterization before an initial randomized dose of lisinopril and again after 12 weeks of maintenance lisinopril therapy. During initial evaluation, lisinopril produced significant decreases in mean systemic arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, mean pulmonary arterial pressure, mean right atrial pressure and pulmonary vascular resistance, and concomitant increases in cardiac index and stroke volume index. After 12 weeks of therapy with lisinopril, the dosage of which was titrated to produce optimal relief of symptoms of congestive heart failure (CHF), repeat hemodynamic studies revealed persistent significant reductions in baseline systemic arterial pressure, pulmonary artery wedge pressure, mean pulmonary arterial pressure and systemic vascular resistance. However, the increases in cardiac index and stroke volume index were not statistically significant. To determine if further acute hemodynamic changes occur during long-term therapy, the patients were readministered a dose of lisinopril. This caused further decreases in systemic arterial pressure, mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance and mean right atrial pressure, and an increase in cardiac index. Lisinopril did not change stroke work index at either initial or rechallenge study. This study indicates that in patients with CHF treated with lisinopril, acute hemodynamic effects persist after 12 weeks of therapy, and acute hemodynamic response continues to occur upon drug readministration.
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PMID:Hemodynamic effects of lisinopril after long-term administration in congestive heart failure. 253 66

After a 2-4 week no-treatment period, 24 patients (12 young, age 29-45 yr.; 12 elderly, age 65-81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91-120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low-dose (10 mg/day) were treated with a high-dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (less than or equal to 90 mm Hg). Low-dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately -15/-8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low-renin patients with essential hypertension.
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PMID:The antihypertensive response to lisinopril: the effect of age in a predominantly black population. 254 Feb 24

Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lisinopril in the treatment of hypertension. 255 Jun 40

In a series of studies, lisinopril, a new, once-daily, non-sulphydryl-containing ACE inhibitor, has been evaluated for the treatment of congestive heart failure (CHF). Lisinopril significantly improved exercise duration, left ventricular ejection fraction (LVEF) and the clinical signs and symptoms of CHF when compared with placebo in a 12-week prospective, randomised, double-blind trial involving 130 patients (NYHA Class II-IV) who were also receiving digitalis and diuretics. In another study involving 10 patients with CHF, lisinopril was found to increase maximal oxygen uptake. Lisinopril has also been compared with captopril in a 12-week randomised, double-blind, parallel trial in 189 patients with CHF (Class II-IV) on digoxin and diuretics. Both lisinopril and captopril increased treadmill exercise times. However, lisinopril was equally effective in patients with renal impairment whereas captopril was not. Also, lisinopril, but not captopril, improved LVEF. In all studies, lisinopril was well tolerated in a manner similar to captopril. Lisinopril produces more frequent increases in serum creatinine than captopril, but these changes are rarely of significant consequence. These results confirm those of previous studies, from which it is concluded that lisinopril is an important addition to the ACE inhibitor class for the treatment of CHF.
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PMID:Lisinopril in the treatment of congestive heart failure. 255 Jun 47

The clearance of drugs excreted entirely unchanged by the kidneys is assumed to relate directly to renal function. The clearance of drugs which are entirely metabolized is usually not altered in patients with renal impairment, although there are examples of both increased and decreased metabolic clearance rates. The clearance of metabolites which are excreted unchanged through the kidneys is also directly related to renal function. The angiotensin converting enzyme (ACE) inhibitors enalapril, ramipril, cilazapril and quinapril are prodrugs that are rapidly converted to active metabolites which are excreted unchanged through the kidneys. Studies have consistently demonstrated reduction in the apparent oral clearance of the active metabolites, in proportion to the degree of impairment of renal function. In addition, for quinapril at least, the metabolic clearance of the parent drug is slightly reduced in renal impairment. The activity of captopril and lisinopril lies in the parent molecule itself. Lisinopril is excreted renally unchanged, while captopril is both metabolized and excreted renally unchanged. The duration of ACE inhibition after administration of any of the ACE inhibitors is prolonged in proportion to the degree of renal impairment. From these pharmacokinetic and pharmacodynamic properties, it follows that the dose rate of the ACE inhibitors should be reduced in direct proportion to the degree of reduction in renal function. Reducing the dose, rather than prolonging the dose interval, is more logical for compliance and for maintaining a consistent degree of ACE inhibition over 24 h.
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PMID:The pharmacokinetics of angiotensin converting enzyme inhibitors in patients with renal impairment. 268 3

1. To elucidate the central effect of lisinopril, a new angiotensin converting enzyme (ACE) inhibitor, ACE localization and levels were followed in the brain of Sprague-Dawley rats by quantitative in vitro autoradiography after administration of the drug. 2. Following acute lisinopril (10 mg/kg p.o.) treatment, serum ACE activity was acutely reduced, but returned to normal by 24 h. 3. Levels of ACE in most parts of the brain, including the basal ganglia and choroid plexus of all ventricles were not affected by lisinopril. Lisinopril inhibited brain ACE in the subfornical organ and organum vasculosum of the lamina terminalis, circumventricular organs, where the blood brain barrier is deficient. These regions are rich in ACE and angiotensin II receptors, and are known targets for angiotensin II-induced effects on fluid, electrolyte and blood pressure homeostasis. 4. These observations indicate that quantitative in vitro autoradiography is a powerful method to study the access of drugs to the central nervous system. 5. This study shows that blood brain barrier plays an important role in limiting the penetration of lisinopril into the central nervous system. The circumventricular organs may be important targets for ACE inhibitors.
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PMID:Blockade of angiotensin converting enzyme in circumventricular organs of the brain after oral lisinopril administration demonstrated by quantitative in vitro autoradiography. 282 4

The interaction of blood pressure, salt intake and the inhibition of angiotensin converting enzyme activity with cardiac hypertrophy were examined in the Dahl rat model. Eight-week-old salt sensitive and salt resistant rats were each separated into two colonies, one of which was maintained on a low salt and the other on a high salt diet for three weeks, at the end of which time both salt sensitive colonies were hypertensive. Each colony was then separated into two groups, one received no medication the other was given lisinopril until normotension was achieved. After 11 weeks of therapy, intra-arterial blood pressures and heart rates were recorded. The rats were sacrificed and heart weight to body weight ratios were determined. Both untreated salt sensitive groups displayed marked cardiac hypertrophy which correlated well with diastolic blood pressure irrespective of salt intake. Lisinopril therapy lowered blood pressures to normotensive levels in all groups except for salt sensitive rats ingesting a high salt diet where, despite a 10-fold increase in drug dose, normotension was not achieved. Significant cardiac regression accompanied lisinopril therapy in rats receiving low salt diets but high salt intake severely attenuated regression in both strains. There was no significant correlation between heart weight and blood pressure in the treated groups. The results suggest that cardiac regression appears to be mediated by other factors besides ventricular afterload pressure and that high salt intake adversely affects blood pressure and heart weight response to lisinopril therapy.
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PMID:Cardiac hypertrophy in experimental hypertension: interaction of the sodium ion, blood pressure and lisinopril. 283 32

Nineteen essential hypertensive patients were entered into a protocol to assess the BP, humoral and renal effects of the angiotensin converting enzyme inhibitor, lisinopril (MK 521, 20 to 80 mg once daily), administered for 52 weeks. Specifically monitored prior to, and following 12 and 52 weeks of lisinopril monotherapy were plasma renin activity and plasma aldosterone, the clearances of creatinine, inulin and para-aminohippurate, and the 24-hour urinary excretion of protein. BP was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed throughout the entire protocol. In contrast to the reported short-term and long-term renal effects of enalapril, lisinopril (a lysine analog of enalapril) had no short-term effect on renal function: glomerular filtration rate, effective renal plasma flow, filtration fraction (FF), renal vascular resistance (RVR), and protein excretion were all unchanged. However, following long-term therapy, both FF and RVR were decreased. Lisinopril appears to convey no specific renal pharmacological benefit.
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PMID:Effect of lisinopril monotherapy on renal hemodynamics. 283 83


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