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:3.4.23.15 (renin)
35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of the angiotensin-converting enzyme (ACE) inhibitor lisinopril on the consequences of myocardial reoxygenation and oxidative damage was assessed in cultured chick embryonic ventricular cardiomyocytes. Lisinopril, 10(-8) M to 10(-6) M, produced a significant (P < 0.05) dose-dependent enhancement of the restoration of contractile frequency occurring during myocardial reoxygenation but did not alter the depression in contractile frequency during hypoxia. Lisinopril significantly (P < 0.05) shifted the dose-response relationship of ammonium persulfate-induced reduction in cardiac contractile frequency. Lisinopril significantly (P < 0.05) reduced the effect of another oxidative agent, tertbutylhydroperoxide which produced a time-dependent reduction in cardiac contractile frequency. Lisinopril did not alter cardiac contractile frequency in the absence of hypoxia or ammonium persulfate or tertbutylhydroperoxide. The viability of cardiomyocytes, assessed by trypan blue exclusion, paralleled the changes in cardiac contractile frequency. Lisinopril significantly (P < 0.05) improved viability of cardiomyocytes exposed to either ammonium persulfate or tertbutylhydroperoxide. Lisinopril did not display any antioxidant properties against the free radical alpha,alpha-diphenyl-beta-picrylhydrazyl. These data suggest that lisinopril accelerates the recovery of cardiomyocytes during reoxygenation and blunts the effects of oxidative agents through mechanisms involving the endogenous renin angiotensin system and/or a direct cellular action.
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PMID:Lisinopril increases the recovery during reoxygenation and resistance to oxidative damage in cardiomyocytes. 840 86

In order to compare the long-term effects on ambulatory blood pressure and left ventricular hypertrophy of hydralazine and lisinopril we studied 30 patients, all males, still hypertensive (diastolic blood pressure > or = 95 mm Hg) despite combined beta-blocker/diuretic therapy and with echocardiographic evidence of left ventricular hypertrophy (left ventricular mass index > or = 1.31 g.m(-1)). They wer randomized to receive hydralazine slow release 50 mg/ chlorthalidone 12.5 mg) for 6 months. Casual blood pressure, non-invasive ambulatory blood pressure monitoring (ABPM), M-mode echocardiogram, plasma renin activity and plasma catecholamines were evaluated before the randomization and after 6 months of treatment. Both drugs significantly reduced casual as well as daytime systolic and diastolic blood pressure, without statistical differences between the two treatments. Lisinopril was significantly more effective than hydralazine in reducing night-time systolic and diastolic blood pressure. Plasma norepinephrine was significantly reduced by lisinopril and increased by hydralazine. Left ventricular mass was significantly reduced by lisinopril but not by hydralazine. The results of linear regression and multiple regression analysis suggested that the lisinopril-induced decrease in both day- and night-time blood pressure might account for the regression of left ventricular hypertrophy, whereas the lack of left ventricular hypertrophy regression during hydralazine treatment could be due mainly to the reflex sympathetic activation induced by the drug.
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PMID:Effects of lisinopril vs hydralazine on left ventricular hypertrophy and ambulatory blood pressure monitoring in essential hypertension. 866 75

In this study we evaluated in hypertensive patients the effects of drug-induced left ventricular hypertrophy regression on cardiac autonomic control, as assessed by means of heart period variability analysis. Power spectral analysis of 24-hour electrocardiographic monitoring was performed in 30 hypertensive patients with left ventricular hypertrophy at baseline, after 1 year of lisinopril treatment, and after 1 month of drug withdrawal. At the same times, patients underwent 24-hour blood pressure monitoring, echocardiographic study, and plasma renin activity assessment. Lisinopril treatment increased plasma renin activity and reduced 24-hour systolic and diastolic pressures (from 159 +/- 14 to 121 +/- 8 and from 103 +/- 7 to 80 +/- 3 mm Hg, respectively) and left ventricular mass index (from 159 +/- 33 to 134 +/- 26 g/m2); moreover, in 12 of 30 patients, left ventricular mass normalization was achieved. Drug withdrawal was followed by an increase in blood pressure without left ventricular mass modification. In the total study population, only high-frequency power was higher after lisinopril treatment. In the subgroup of patients with left ventricular mass normalization, daytime and nighttime high-frequency powers as well as nighttime total and very-low-frequency powers were higher after 1 year of treatment than at baseline. In the remaining 18 patients, power spectral measures after treatment were slightly lower than at baseline and were even lower after drug withdrawal. Thus, in hypertensive hypertrophic patients, lisinopril treatment improves sympathovagal imbalance when left ventricular mass normalization is achieved. In patients without left ventricular mass normalization, drug withdrawal is followed by a worsening of neural cardiac control.
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PMID:Effect of 1 year of lisinopril treatment on cardiac autonomic control in hypertensive patients with left ventricular hypertrophy. 869 34

We studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p < 0.005) with a progressive increase in the rapid filling dV/dt (p < 0.005 at rest; p < 0.001 during CPT) and a reduction in isovolumetric relaxation (p < 0.0001 at rest and p < 0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal (reduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.
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PMID:Left ventricular diastolic function during adrenergic stress in essential hypertension: acute and chronic effects of ACE inhibition. 887 75

The transgenic rat (TGR) (mRen-2)27 is said to have low circulating active renin values in plasma and little or no renin gene expression in the kidney. Nevertheless, intrarenal angiotensin II-related effects appear to be responsible for the rightward shift in pressure-natriuresis curves of TGR. To clarify the role of the intrarenal renin-angiotensin system in modulating TGR pressure-natriuresis, TGR were given lifelong lisinopril by treating TGR and their mothers before conception. Rat and mouse renin, AT1 receptor, and angiotensinogen gene expression in the kidneys were studied with in situ hybridization. Neural and endocrine regulatory differences between TGR and Sprague-Dawley Hannover (SDH) rats were eliminated by renal denervation and infusion of vasopressin, aldosterone, 17-OH corticosterone, and norepinephrine. TGR with lisinopril had blood pressures similar to SDH. In TGR with lisinopril, the pressure-natriuresis curve was shifted leftward but not quite to the values observed in SDH given lisinopril. The histology of lisinopril-treated TGR was indistinguishable from normal SDH. Lisinopril increased rat renin and angiotensinogen gene expression both in SDH and TGR, but it did not influence mouse renin gene expression in TGR. Discontinuing lisinopril increased blood pressure in TGR and shifted the pressure-natriuresis relationship rightward. Thus, the components of the endogenous renin-angiotensin system and the mouse renin transgene were present and expressed in kidneys of TGR. The rat gene components responded to lisinopril as expected, but the mouse renin transgene expression was not influenced. Lisinopril normalized TGR blood pressure; however, a detectable leftward shift in pressure-natriuresis remained. These studies underscore the role of angiotensin-mediated effects of the mouse renin transgene in terms of shifting pressure-natriuresis in TGR.
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PMID:Lifelong angiotensin-converting enzyme inhibition, pressure natriuresis, and renin-angiotensin system gene expression in transgenic (mRen-2)27 rats. 891 71

LVH AND RISK: Left ventricular hypertrophy (LVH) is a powerful predictor of cardiovascular morbidity and mortality, independent from blood pressure and other cardiovascular risk factors. Available data indicate that patients who fail to achieve a reduction in LVH are much more likely to suffer cardiovascular events than those in whom LVH is reduced or even normalized using antihypertensive treatment. Reversal of LVH, therefore, represents a major goal in the treatment of hypertensive patients. REGRESSION OF LVH: Since obesity and dietary sodium intake may modulate the degree of LVH, non-pharmacological intervention has achieved a successful reduction in left ventricular mass (LVM). LVM is more closely related to 24-h blood pressure values than to clinical blood pressure values. Recent evidence from the Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation has shown that the regression of cardiac hypertrophy is predicted to a greater degree by the effect of antihypertensive treatment on 24-h average blood pressure than by that on clinic or home blood pressure. The increase in blood pressure variability may also be an independent determinant of cardiovascular target-organ damage, particularly of cardiac hypertrophy. However, the effects of antihypertensive drugs on blood pressure variability can be difficult to determine, mainly because a correct measurement of variability requires a beat-to-beat measurement of ambulatory blood pressure; several measures have been proposed to evaluate the smoothness of blood pressure control during antihypertensive treatment. Other important determinants of LVH reduction are represented by baseline values of LVM, extent of blood pressure reduction and duration of treatment. Furthermore, the degree of cardiac hypertrophy reduction is not the same for the different classes of antihypertensive drugs because, beyond the control of blood pressure, they may interfere differently with several non-haemodynamic stimuli, including the renin-angiotensin-aldosterone and the adrenergic systems or other growth factors. A more pronounced reduction in LVM with angiotensin converting enzyme inhibitors and calcium antagonists has been demonstrated in several recent meta-analyses. The results of further multicenter on-going trials are awaited to evaluate definitely whether various antihypertensive strategies differ in their ability to reverse LVH and to adequately assess the relationship between changes in LVM and subsequent prognosis, with serial control of blood pressure values measured in the clinic and by ambulatory monitoring.
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PMID:Left ventricular hypertrophy: how to influence an important risk factor in hypertension. 953 98

The (mRen2)27 transgenic rat [TGR(mRen2)27] is said to have low plasma levels of active renin. We used a direct radioimmunoassay (RIA) for mouse submaxillary renin, as well as an indirect enzyme-kinetic assay based on the generation of angiotensin I with modification of the pH optimum, to measure rat and mouse plasma renin activity (PRA), plasma renin concentration (PRC), and plasma prorenin in TGR before and after lisinopril. The relationship between rat PRC and % rat kidney extract was steepest at pH 6.0 and flat at pH 8.5, whereas the relationship between mouse PRC and purified mouse renin was steepest at pH 8.5 and flat at pH 6.0. Mouse PRC was highly correlated with direct RIA measurements (r = 0.93). PRA before lisinopril was little influenced by pH, whereas the increase with lisinopril was greatest at pH 6.5. PRC before lisinopril was fourfold higher at pH 8.5 compared with that at pH 6.0. Lisinopril increased both PRC values but reversed the pH dependency. Prorenin was fourfold higher at pH 8.5 compared with that at pH 6.0 and decreased slightly with lisinopril. Renal renin concentration was higher at pH 6.0 than at pH 8.5. With lisinopril, renal renin concentration increased at both pH values. Mouse PRC was not changed by lisinopril. Ribonuclease protection assay showed both rat and mouse renin gene expression in the kidney, which increased with lisinopril. Thus TGR have circulating active rat and mouse renin and prorenin. The notion that TGR are a "low renin" model should be revised.
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PMID:Mouse and rat plasma renin concentration and gene expression in (mRen2)27 transgenic rats. 961 49

We determined the mechanism accounting for the removal and metabolism of angiotensin-(1-7) [Ang-(1-7)] in 21 anesthetized spontaneously hypertensive (SHR), 18 age-matched normotensive Sprague-Dawley (SD), and 36 mRen-2 transgenic (TG+) rats. Animals of all 3 strains were provided with tap water or tap water containing losartan, lisinopril, or a combination of lisinopril and losartan for 2 weeks. On the day of the experiment, Ang-(1-7) was infused for a period of 15 minutes at a rate of 278 nmol . kg-1 . min-1. After this time, samples of arterial blood were collected rapidly at regular intervals for the assay of plasma Ang-(1-7) levels by radioimmunoassay. Infusion of Ang-(1-7) had a minimal effect on vehicle-treated SD rats but elicited a biphasic pressor/depressor response in vehicle-treated SHR and TG+ rats. In lisinopril-treated rats, Ang-(1-7) infusion increased blood pressure, whereas losartan treatment abolished the pressor component of the response without altering the secondary fall in arterial pressure. Combined treatment with lisinopril and losartan abolished the cardiovascular response to Ang-(1-7) in all 3 strains. In vehicle-treated SD, SHR and TG+ the half-life (t1/2) of Ang-(1-7) averaged 10+/-1, 10+/-1, and 9+/-1 seconds, respectively. Lisinopril alone or in combination with losartan produced a statistically significant rise in the half-life of Ang-(1-7) in all 3 strains of rats. Plasma clearance of Ang-(1-7) was significantly greater in the untreated SD rats compared with either the SHR or TG+ rat. Lisinopril treatment was associated with reduced clearance of Ang-(1-7) in all 3 strains. Concurrent experiments in pulmonary membranes from SD and SHR showed a statistically significant inhibition of 125I-Ang-(1-7) metabolism in the presence of lisinopril. These studies showed for the first time that the very short half-life of Ang-(1-7) in the circulation is primarily accounted for peptide metabolism by ACE. These findings suggest a novel role of ACE in the regulation of the production and metabolism of the two primary active hormones of the renin angiotensin system.
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PMID:Converting enzyme determines plasma clearance of angiotensin-(1-7). 974 Jun 16

The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and enalapril, alone and in combination with propranolol were studied. In an open, randomised, cross-over design 12 healthy volunteers received orally enalapril 20 mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma angiotensin-converting enzyme activity and plasma renin activity were measured for 24 h after each treatment period. Lisinopril and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, P<0.05) and 12 hr (-65%, P<0.05), irrespective of combination with propranolol. At 24 hr plasma angiotensin-converting enzyme activity remained significantly suppressed only after lisinopril (-60%, P<0.05). Plasma renin activity increased almost ten times after ingestion of both angiotensin-converting enzyme inhibitors, but the effect lasted significantly longer after lisinopril than after enalapril. Beta-Adrenergic blockade blunted the effect on the increase in plasma renin activity induced by both angiotensin-converting enzyme inhibitors. Our results show that the effect of lisinopril on plasma angiotensin-converting enzyme activity and plasma renin activity lasted longer than that of enalapril. beta-Adrenergic blockade suppressed the effect on elevated plasma renin activity, but did not influence the effect of angiotensin-converting enzyme inhibitors on plasma angiotensin-converting enzyme activity.
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PMID:Effects on plasma angiotensin-converting enzyme activity and circulating renin of lisinopril and enalapril alone and in combination with propranolol in healthy volunteers. 1019 70

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.
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PMID:Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects. 1037 65


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