UMLS:C0011881 - FACTA Search

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

Query: UMLS:C0011881 (diabetic nephropathy)
10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An open, randomized, cross-over study was undertaken to assess the effects of lisinopril and nifedipine on albumin excretion, renal haemodynamics and segmental tubular reabsorption in overt diabetic nephropathy. The study consisted of a 4-week run-in period, a 3-week active treatment period, a 4-week wash-out period and a second 3-week active treatment period. Twelve patients with type 1 diabetes with albuminuria, mild to moderate hypertension and a serum creatinine level of less than 200 mumol l-1 were included. Lisinopril reduced albumin excretion from 1343 +/- 337 micrograms min-1 to 879 +/- 299 micrograms min-1 (P less than 0.01), whereas nifedipine was without effect, 1436 +/- 336 micrograms min-1 vs. 1319 +/- 342 micrograms min-1. Glomerular filtration rate (GFR) was unchanged by either drug. Both drugs increased effective renal plasma flow (ERPF) by about 20%. No differences between the drugs were observed with regard to their effect on renal haemodynamic parameters. By contrast, nifedipine exerted an inhibitory effect on several proximal tubular transport markers, whereas lisinopril was without effect. The different actions on tubular transport mechanisms exerted by lisinopril and nifedipine may contribute to the observed effect on albumin excretion.
...
PMID:Contrasting effects of lisinopril and nifedipine on albuminuria and tubular transport functions in insulin dependent diabetics with nephropathy. 184 21

Angiotensin converting enzyme (ACE) inhibitors are now widely used for the treatment of hypertension and heart failure. They are of particular value in treating hypertensive patients with left ventricular dysfunction, and in diabetics where they have been shown to delay the progression of diabetic nephropathy. Differences in the metabolism, pharmacokinetics, and pharmacodynamics between the various ACE inhibitors generally do not translate into significant clinical differences in the majority of patients. However, fosinopril may be the preferred ACE inhibitor in patients with significant renal dysfunction because of a reduced requirement for dosage reduction. The duration of action of ACE inhibitors is determined by two properties, the plasma half-life and the affinity of binding to tissue ACE. All of the ACE inhibitors (with the possible exception of captopril) can provide satisfactory 24-hour blood pressure control in the majority of patients with mild to moderate hypertension when given once daily. Lisinopril provides consistently better 24-hour control of blood pressure than either captopril or enalapril. Evidence for superior 24-hour blood pressure control over enalapril has not been as well established for the other ACE inhibitors. Captopril may be preferred for initiating therapy in patients with severe heart failure who are at risk of first dose hypertension because of its rapid onset of action and relatively short duration of action. There is evidence, however, that perindopril may have a low risk of first dose hypertension in heart failure because of its gradual onset of action. Long-acting ACE inhibitors may be preferable for chronic therapy of heart failure. All of the ACE inhibitors have a low incidence of adverse effects in both young and elderly patients, and there is no convincing evidence of differences in tolerability between the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Critical assessment of ACE inhibitors. Part 2. 777 72

Lisinopril, the lysine analogue of enalaprilat, is a long-acting angiotensin converting enzyme (ACE) inhibitor which is administered once daily by mouth. The efficacy of lisinopril in reducing blood pressure is well established in younger populations, and many trials now show it to be effective in lowering blood pressure in elderly patients with hypertension. In comparative and non-comparative clinical trials, 68.2 to 89.1% of elderly patients responded (diastolic pressure < or = 90 mm Hg) to > or = 8 weeks' lisinopril treatment. Age-related differences in antihypertensive efficacy do not appear to be clinically significant, and dosages effective in elderly patients tend to range from 2.5 to 40 mg/day. Dosages usually need to be lower in patients with significant renal impairment. In congestive heart failure, lisinopril 2.5 to 20 mg/day increases exercise duration, improves left ventricular ejection fraction and has no significant effect on ventricular ectopic beats. It is similar in efficacy to enalapril and digoxin and similar or superior to captopril on most end-points. Data from the GISSI-3 post-myocardial infarction trial show that lisinopril reduced mortality and left ventricular dysfunction when given for 42 days starting within 24 hours of the onset of infarction symptoms. Results at 6 weeks and 6 months were similar in elderly and younger patients. Elderly patients, however, among other subgroups, exhibited a strong reduction in risk of low ejection fraction after treatment (-25.5%). Economic studies suggest that lisinopril is cost saving compared with other ACE inhibitors in some markets. When given according to the GISSI-3 protocol, lisinopril appears to be one of the less expensive of the successful ACE inhibitor regimens for acute myocardial infarction. In other trials, patients with diabetic nephropathy and hypertension improved or did not deteriorate during lisinopril treatment. Blood pressure was controlled and reductions or trends towards reductions in albuminuria were observed. These reductions were similar to those in diltiazem, nifedipine and verapamil recipients, and greater than those in patients receiving atenolol. Lisinopril appears to reduce mortality in diabetic patients after myocardial infarction and may also improve neuropathy associated with diabetes. Lisinopril is well tolerated and the profile of adverse events seen is typical of ACE inhibitors as a class. There is a tendency for more elderly than younger patients to discontinue treatment, but this trend is not clearly related to the incidence of adverse events in these age groups. Drug interactions occur with few other agents and are usually clinically significant only between lisinopril and either diuretics or lithium. Lisinopril is, thus, an effective treatment for elderly patients with hypertension, congestive heart failure and acute myocardial infarction and has shown promising benefits in patients with diabetic nephropathy.
...
PMID:Lisinopril. A review of its pharmacology and clinical efficacy in elderly patients. 906 Dec 70

Chronic nephropathies are associated with enhanced renal synthesis of endothelin (ET)-1. A recent study demonstrated that an ET(A) receptor antagonist given to diabetic rats at the moment of disease induction prevented the development of renal injury. Here we investigated whether an unselective ET(A)/ET(B) receptor antagonist, PD 142,893, was renoprotective when given to streptozotocin diabetic rats when animals were already proteinuric. The effect of PD 142,893 was compared with that of an ACE inhibitor, lisinopril, known to retard progressive renal disease in experimental and human diabetes. PD 142,893 normalized systemic blood pressure, reduced urinary protein and albumin excretion, and ameliorated renal blood flow in diabetic rats, but it did not affect such parameters in control rats. Lisinopril had a renoprotective effect comparable to PD 142,893, although lisinopril controlled systemic blood pressure better. Northern blot analysis of ET-1 mRNA revealed upregulation of ET-1 gene in the diabetic kidney. Similar results were obtained by in situ hybridization in glomeruli and tubuli of diabetic rats. Both treatments remarkably attenuated exaggerated renal ET-1 gene expression. These data suggest that ET-1 is a contributory mediator of kidney damage in diabetes and indicate that ET receptor antagonists may represent a new therapeutic mean for treatment of progressive diabetic nephropathy.
...
PMID:Unselective inhibition of endothelin receptors reduces renal dysfunction in experimental diabetes. 951 53

1. Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) compared with an angiotensin-converting enzyme inhibitor (lisinopril) on the non-neurogenic regulation of the microvascular blood flow in hypertensive Type I diabetes patients with diabetic nephropathy.2. We performed a 1-year double-blind, double-dummy randomized controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 48 hypertensive Type I diabetes patients with diabetic nephropathy. For comparison, 22 age-matched normotensive healthy control subjects were included. Measurements were performed at baseline and after 1 year of antihypertensive treatment. The minimal vascular resistance and distensibility (stiffness) of resistance vessels in skin and skeletal muscle were measured using the local isotope washout method.3. Mean arterial pressure was reduced to the same extent in both groups: nisoldipine, 113+/-2.1 to 105+/-1.6 mmHg (P<0.001); lisinopril, 110+/-2.7 to 101+/-2.1 mmHg (P<0.002) (controls, 88+/-2.2 mmHg; P<0.0001 compared with diabetic patients). Nisoldipine improved the skin vascular distensibility from 28+/-3.3 to 43+/-3.8% (P<0.005) and decreased skin minimal vascular resistance from 16.9+/-1.0 to 13.6+/-0.8 mmHg.ml-1.min.100 g (P<0. 02). Lisinopril had no significant effect on skin vascular distensibility (40+/-4.0% and 41+/-4.4%), but minimal vascular resistance tended to diminish (18.1+/-0.9 to 15.8+/-1.3 mmHg.ml-1. min.100 g (P=0.09). Nisoldipine significantly increased the skin distensibility (P=0.05) after 1 year of antihypertensive treatment compared with lisinopril.4. The control group had a skin vascular distensibility of 54+/-3.2% and a minimal vascular resistance of 10. 8+/-0.7 mmHg.ml-1.min.100 g, both significantly different from the values in the diabetic groups (P<0.0001 for all). Skeletal muscle vascular distensibility was unaltered after 1 year of treatment with both nisoldipine (22+/-3.3% and 19+/-2.7%) and lisinopril (19+/-2.1% and 24+/-2.5%), but was reduced compared with a control value of 43+/-3.7% (P<0.0001 for diabetes patients versus controls). However, neither nisoldipine nor lisinopril had any effect on the increased minimal vascular resistance or the reduced skeletal muscle distensibility.5. Enhanced thickening of the basement membranes of the terminal arteriolar wall was found in skin biopsy specimens in 91% of diabetic patients and 38% only in control subjects (P<0. 000001 both before and after treatment for diabetic patients versus controls). There was no significant effect of antihypertensive treatment on arteriolar hyalinosis.6. The reduction in systemic blood pressure was identical during 1 year of treatment with nisoldipine or lisinopril. The abnormal arteriolar stiffness was more pronounced in the group treated with nisoldipine than with lisinopril and only nisoldipine compared with lisinopril improved the abnormal arteriolar stiffness and minimal vascular resistance in the skin. This suggests that nisoldipine can reverse the peripheral skin perfusion and thereby improve the local protection against development of ischaemic skin lesions in Type I diabetes patients with clinical diabetic nephropathy.
...
PMID:Effects of nisoldipine and lisinopril on microvascular dysfunction in hypertensive Type I diabetes patients with nephropathy. 983 96

Inhibitors of angiotensin converting enzyme (ACE inhibitors) have been introduced more than fifteen years ago into the treatment of hypertension, congestive heart failure, myocardial infarction and diabetic nephropathy. The therapeutic success is related to their action in reduction of plasma and tissue angiotensin II concentrations and potentiation of endogenous kinins. They are able to improve myocardium metabolic status, prevent cardiac hypertrophy, limit myocardial infarct size, and thus prevent heart failure. Since 1987 ACE inhibitors are introduced in the clinical practice in our clinic. We introduced the therapy with lisinopril (Lopril), in 70% of patients among 2855 patients that were admitted in Coronary Care Unit in 1997 and 1998. Lisinopril was introduced as soon as the patient was admitted, together with fibrinolitic, Heparin and Aspirin therapy. Since that time we noticed decrease in postinfarction heart failure in comparison to previous years. We recommend permanent therapy with a small doses of ACE inhibitors in patients with heart infarction.
...
PMID:[Converting enzyme inhibitors in acute myocardial infarct and heart failure]. 1035 28

The angiotensin converting enzyme (ACE) inhibitors are widely used in the management of essential hypertension, stable chronic heart failure, myocardial infarction (MI) and diabetic nephropathy. There is an increasing number of new agents to add to the nine ACE inhibitors (benazepril, cilazapril, delapril, fosinopril, lisinopril, pentopril, perindopril, quinapril and ramipril) reviewed in this journal in 1990. The pharmacokinetic properties of five newer ACE inhibitors (trandolapril, moexipril, spirapril, temocapril and imidapril) are reviewed in this update. All of these new agents are characterised by having a carboxyl functional groups and requiring hepatic activation to form pharmacologically active metabolites. They achieve peak plasma concentrations at similar times (t(max)) to those of established agents. Three of these agents (trandolapril, moexipril and imidapril) require dosage reductions in patients with renal impairment. Dosage reductions of moexipril and temocapril are recommended for elderly patients, and dosages of moexipril should be lower in patients who are hepatically impaired. Moexipril should be taken 1 hour before meals, whereas other ACE inhibitors can be taken without regard to meals. The pharmacokinetics of warfarin are not altered by concomitant administration with trandolapril or moexipril. Although imidapril and spirapril have no effect on digoxin pharmacokinetics, the area under the concentration-time curve of imidapril and the peak plasma concentration of the active metabolite imidaprilat are decreased when imidapril is given together with digoxin. Although six ACE inhibitors (captopril, enalapril, fosinopril, lisinopril, quinapril and ramipril) have been approved for use in heart failure by the US Food and Drug Administration, an overview of 32 clinical trials of ACE inhibitors in heart failure showed that no significant heterogeneity in mortality was found among enalapril, ramipril, quinapril, captopril, lisinopril, benazepril, perindopril and cilazapril. Initiation of therapy with captopril, ramipril, and trandolapril at least 3 days after an acute MI resulted in all-cause mortality risk reductions of 18 to 27%. Captopril has been shown to have similar morbidity and mortality benefits to those of diuretics and beta-blockers in hypertensive patients. Captopril has been shown to delay the progression of diabetic nephropathy, and enalapril and lisinopril prevent the development of nephropathy in normoalbuminuric patients with diabetes. ACE inhibitors are generally characterised by flat dose-response curves. Lisinopril is the only ACE inhibitor that exhibits a linear dose-response curve. Despite the fact that most ACE inhibitors are recommended for once-daily administration, only fosinopril, ramipril, and trandolapril have trough-to-peak effect ratios in excess of 50%.
...
PMID:Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. 1192 21

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
...
PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

This study was carried out to assess whether with a similar degree of blood pressure reduction, Lisinopril compares favorably or otherwise with lacidipine in respect of effects on urinary albumin excretion and renal function as assessed by creatinine clearance, plasma creatinine, urea and electrolytes. Thirty hypertensive diabetic nephropathy patients with moderate hypertension were studied. After a 2-week washout period, they were allocated into two groups matched at baseline for age, sex, weight, blood pressure, and urinary albumin excretion rate as well as creatinine clearance. There were 8 males and 7 females in each group. One group received lisinopril (with furosemide if needed to control BP) and the other group received lacidipine. Staged increases in doses of antihypertensives were used until BP was controlled or maximum dose of 40 mg/day lisinopril or 8 mg/day lacidipine was reached. Furosemide was added to lisinopril if BP was not controlled at 40 mg/day. These medications were given for 12 weeks at the end of which measurements done at baseline were repeated. Comparison of baseline and end of study values of these parameters within the groups and between the two groups were made. Lisinopril group and lacidipine group achieved similar and highly significant reduction in blood pressure levels P < 0.001. There was reduction in urinary albumin excretion rate in both groups but this only reached statistical significance in the lisinopril group [480] [269] mg/day vs. 315 [202] mg/day P < 0.05] while for the lacidipine group it was not significant [491] [257] mg/day vs. 335 [182] mg/day P > 0.05]. However, comparison of albumin excretion rate between both groups at baseline and at end of the study did not show any significant difference, P > 0.1. With both drugs there is a tendency for creatinine clearance to increase and plasma creatinine to drop while plasma potassium tended to rise more with lisinopril than lacidipine but differences within and between both groups, did not reach statistical significance P > 0.05. In conclusion, blood pressure reduction was comparable in both drugs; both drugs reduced albuminuria but lisinopril appeared superior. Treatment with both drugs tended to increase creatinine clearance but both had no significant effects on blood sugar.
...
PMID:Comparative effect of lisinopril and lacidipine on urinary albumin excretion in patients with type 11 diabetic nephropathy. 1251 31

Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles.
...
PMID:Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. 1254 Aug 54

1 2 Next >>