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)

Gelatinases are metalloproteinases in the kidney which can cleave type IV collagen as well as gelatin. We partially purified the 72 kDa and 92 kDa gelatinases. The gelatinolytic activity was measured by zymography and a quantitative biotin-avidin assay. By zymography, captopril in concentrations of 20 mM and 40 mM added to the incubation buffer reduced the gelatinolytic activity in a dose-dependent manner. The addition of zinc in a concentration of 50 to 100 microM reversed most of the inhibitory effect of captopril. By the biotin-avidin assay, captopril in a concentration of 30 to 50 nM reduced half of either the 72 kDa or 92 kDa gelatinolytic activity. Zinc in a concentration of 50 microM completely reversed the inhibitory effect of 1 microM captopril on both gelatinases. Lisinopril, a non-sulfhydryl ACE inhibitor, similarly inhibited the gelatinases, but a 100-fold higher concentration of the drug was needed. These findings suggest that captopril reversibly inhibits the 72 kDa and 92 kDa metalloproteinases by interacting with the zinc ion at their active sites. This inhibitory effect is observed with captopril levels comparable to the concentrations needed to inhibit the angiotensin converting enzyme in vivo and may at least partially explain some of the renoprotective effects seen with this drug.
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PMID:Captopril inhibits the 72 kDa and 92 kDa matrix metalloproteinases. 830 28

Although lisinopril and enalapril are equipotent angiotensin converting enzyme (ACE) inhibitors lisinopril has been reported to produce greater inhibition of plasma ACE 24 hours after single doses. This study compared the antihypertensive effects of once daily 10mg doses of the drugs using a randomised, double-blind, two period cross-over design with ambulatory blood pressure monitoring. Lisinopril lowered mean 24 hour systolic blood pressure significantly more than enalapril after 4 weeks of treatment (14/7 +/- 2/1mmHg & 9/6 +/- 2/1mmHg, respectively, adjusted SBP difference 4.8mmHg, P < 0.01). This difference was confined to the second 12 hours of the daily dosage interval (adjusted SBP difference 13-24 hours after dosing 9.9mmHg, P < 0.001). The diastolic pressure showed a similar trend but this was not statistically significant. The side effects of each agent were minor. We conclude that chronic, once daily therapy with 10mg of lisinopril reduces systolic blood pressure more effectively than an equal dose of enalapril due to its greater effect in the latter half of the 24 hour dosage interval.
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PMID:Differences in the acute and chronic antihypertensive effects of lisinopril and enalapril assessed by ambulatory blood pressure monitoring. 838 25

Hyperinsulinaemia and insulin resistance are associated with essential hypertension irrespective of obesity and non-insulin-dependent diabetes mellitus. One of the mechanisms whereby hyperinsulinaemia may play a role in the increase in blood pressure, is an increased activity of the sympathetic nervous system. The authors studied the incidence of hyperinsulinaemia, and the possibility of modulating it by 12-week administration of the ACE inhibitor (ACEI) lisinopril (Prinivil by MSD) at a dose of 20-40 mg/day. Compared with normotensive subjects, hypertensives showed a degree of hyperinsulinaemia and insulin resistance (higher blood glucose at higher immunoreactive insulin and C-peptide concentrations, and a higher IRI/blood glucose ratio) as well as manifestations of enhanced sympathetic activity (higher adrenaline levels). Lisinopril had a favourable effect not only on blood pressure but, also, on hyperinsulinaemia and adrenaline levels. It can be reasonably concluded that therapy with ACEI, in addition to its antihypertensive effect, may also favourably modulate some pathogenic and metabolic factors in essential hypertension.
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PMID:[Control of hyperinsulinemia in essential hypertension using the angiotensin-converting enzyme inhibitor, lisinopril]. 838 86

The effect of treatment of rats with the angiotensin converting enzyme inhibitor lisinopril after 5 weeks of untreated streptozotocin-diabetes was examined by daily monitoring of sciatic motor conduction velocity to tibialis anterior muscle. Diabetes produced a 31.5% decrease in conduction velocity (P < 0.001). Lisinopril treatment caused a progressive improvement which was significant after 3 days (P = 0.002), full normalization being achieved by 6 days (P < 0.0001). After 7 days of treatment there followed a 7-day washout period in which no lisinopril was given. During this time conduction velocity declined to untreated diabetic levels over 3 days. A subsequent treatment period resulted in complete normalization of conduction velocity within 2 days (P < 0.0001). Thus, the marked functional effects seen for vasodilator treatment with lisinopril suggest that angiotension converting enzyme inhibitors may have potential therapeutic value in the treatment of diabetic neuropathy.
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PMID:Rapid reversal of a motor nerve conduction deficit in streptozotocin-diabetic rats by the angiotensin converting enzyme inhibitor lisinopril. 839 3

Patients with congestive cardiac failure have elevated sympathetic activity at rest which contributes to the pathophysiology of this syndrome. In addition, the sympathetic response to exercise in these patients is abnormal. Sympathetic activity is accurately reflected by serum noradrenaline levels. In a double-blind, placebo-controlled, parallel group study, 16 patients of New York Heart Association (NYHA) functional class II, stabilised on optimum doses of diuretics were randomised into two equal groups, to receive either low-dose Lisinopril, an orally active angiotensin converting enzyme (ACE) inhibitor, or matching placebo, over a 12 week period. At the end of the 12 week treatment phase, there was no significant change in noradrenaline levels at rest (p = 0.33) mid exercise (p = 0.17), or peak exercise (p = 0.69), in the lisinopril group. Both lisinopril and placebo groups improved subjectively as assessed by change in NYHA grade, (p < 0.01 for placebo and p < 0.001 for those given lisinopril). Exercise duration improved significantly in the lisinopril group (p = 0.0296), but not in the placebo group after treatment. Low dose lisinopril is of use in congestive cardiac failure even in the absence of measurable changes in sympathetic tone.
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PMID:The effects of lisinopril on serum catecholamine concentrations both at rest and on exercise in patients with congestive cardiac failure. A double blind, placebo controlled, parallel group study. 839 88

It has been reported that the urinary excretions of chloride (Cl), potassium (K), and magnesium (Mg), but not sodium (Na), after furosemide, a loop diuretic, were decreased by pretreatment with lisinopril, an ACE inhibitor in hypertensive subjects. The electrolytes disturbance induced by furosemide might be ameliorated by lisinopril. The present study re-examines this potential drug interaction in healthy subjects. Lisinopril (20 mg) or its matching placebo was given orally using a double-blind, crossover design. Four hours after lisinopril administration, furosemide (20 mg) was injected intravenously and urine was collected during the following intervals: 0-0.5, 0.5-1, 1-1.5, 1.5-2, 2-3, 3-4, and 4-6 hours. Blood samples for plasma furosemide concentration were obtained at 0.5, 1, 1.5, 2, 3, 4, and 6 hours after the agent. There were no significant differences between the two trials in plasma concentrations of furosemide or urinary excretions of the agent. Urine volume and urinary excretions of electrolytes (Na, Cl, K, and Mg) after the furosemide with lisinopril administration were not significantly different from those of placebo at any observation period. These results suggest that the urinary excretions of electrolytes after furosemide administration are not influenced by pretreatment with lisinopril.
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PMID:Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects. 839 58

A total of 3463 hypertensive patients with type II diabetes were treated with lisinopril for 3 months. Lisinopril was well tolerated, adverse effects were observed in only 2.2% of the patients. Blood pressure values were effectively reduced by lisinopril, two-thirds of the patients could be treated with lisinopril monotherapy. Parameters of metabolic control (HbA1c, lipids) showed an overall improvement under lisinopril therapy. Serum levels of creatinine did not change in patients who were with normal pretreatment values, but were normalized in approximately 50% of patients with elevated pretreatment values. It can be concluded that under routine medical care ACE inhibitor lisinopril is a well tolerated, effective drug for treatment of hypertensive type II diabetic patients.
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PMID:Effects of ACE inhibitors on renal function in incipient and overt diabetic nephropathy. 880 57

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be started within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries reflects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with left ventricular dysfunction. The choice of ACE inhibitor appears less important than the decision to treat; it seems likely that these benefits are a class effect. Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost analyses are flawed and this latter points remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisinopril (within 24 hours of symptom onset) for 6 weeks improves survival and reduces cardiovascular morbidity in patients with myocardial infarction, and confers ongoing benefit after drug withdrawal. While patients with symptoms of left ventricular dysfunction are prime candidates for treatment, all those who are haemodynamically stable with no other contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to be beneficial should therefore be considered an integral part of the early management of myocardial infarction in suitable patients.
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PMID:Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction. 889 68

Recent studies have shown that angiotensin-(1-7) [Ang-(1-7)] interacts with kinins and augments bradykinin (BK)-induced vasodilator responses by an unknown mechanism. In this study, we evaluated whether the potentiation of the BK-induced vasodilation by Ang-(1-7) may be attributable to inhibition of BK metabolism, release of nitric oxide, or both. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers. 125I-[Tyr0]-BK metabolism was determined in vascular rings by assessing the degradation of the peptide by high-performance liquid chromatography. Ang-(1-7) augmented the vasodilation induced by BK in a concentration-dependent manner in rings preconstricted with the thromboxane analog U46619. The EC50 of BK (2.45 +/- 0.51 nmol/L versus 0.37 +/- 0.08 nmol/L) was shifted leftward by 6.6-fold in the presence of 2 mumol/L concentration of Ang-(1-7). The response was specific for BK. since Ang-(1-7) did not augment the vasodilation induced by either acetylcholine (0.05 mumol/L) or sodium nitroprusside (0.1 mumol/L). Moreover, neither angiotensin I nor angiotensin II (Ang II) duplicated the augmented BK response of Ang-(1-7). Pretreatment of vascular rings with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NA; 100 mumol/L) completely abolished the effects of Ang-(1-7) on BK-induced vasodilation whereas pretreatment with indomethacin (10 mumol/L) was without effect. The potent specific BK B2 receptor antagonist, Hoe 140. nearly abolished the BK and the Ang-(1-7) potentiated responses at 2 mumol/L, whereas at a lower concentration (20 nmol/L) Hoe 140 shifted the response curve to the right for both Ang-(1-7) and vehicle; however, the augmented response to Ang-(1-7) persisted. Preincubation of vascular rings with 20 mumol/L of the AT1 (CV11974), AT2 (PD123319), or nonselective (Sar1 Thr8-Ang II) receptor antagonists had no significant effect on the Ang-(1-7)-enhanced vasodilator response to BK. Lisinopril (2 mumol/L) significantly enhanced the BK-induced vasodilator response while at the same time it abolished the synergistic action of Ang-(1-7) on BK. In addition, pretreatment with 2 mumol/L Ang-(1-7) significantly inhibited the degradation of 125I-[Tyr0]-BK and the appearance of the BK-(1-7) and BK-(1-5) metabolites in coronary vascular rings. Ang-(1-7) inhibited purified canine angiotensin converting enzyme activity with an IC50 of 0.65 mumol/L. In conclusion. Ang-(1-7) acts as a local synergistic modulator of kinin-induced vasodilation by inhibiting angiotensin converting enzyme and releasing nitric oxide.
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PMID:Angiotensin-(1-7) augments bradykinin-induced vasodilation by competing with ACE and releasing nitric oxide. 903 33

The aim of the present study was to determine whether or not the pharmacokinetic and hemodynamic response to a 20 mg single oral dose of lisinopril was sex-dependent. Thirty-two young healthy volunteers (16 males and 16 females) were included in the trial. Blood samples to assess lisinopril plasma concentrations, determined indirectly by inhibition of the angiotensin converting enzyme (ACE) and hemodynamic variables, were obtained before and at different times following drug intake. No significant differences in pharmacokinetic parameters were observed between males and females. An hypotensive response was obtained between 2 and 10 h for systolic blood pressure and between 2 and 24 h for diastolic blood pressure. Again, no significant sex-related differences were noted. Lisinopril was well tolerated.
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PMID:Sex-related pharmacokinetic and pharmacodynamic variations of lisinopril. 904 42


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