Home About us Contact
|
Home About us Contact | ||
|
|
||
Enzyme Inhibitors (enzyme + inhibitor)
Kinds of Enzyme Inhibitors Selected AbstractsSPIRONOLACTONE FURTHER REDUCES URINARY ALBUMIN EXCRETION AND PLASMA B-TYPE NATRIURETIC PEPTIDE LEVLES IN HYPERTENSIVE TYPE II DIABETES TREATED WITH ANGIOTENSIN-CONVERTING ENZYME INHIBITORCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006Susumu Ogawa SUMMARY 1Over the course of treatment with angiotensin-converting enzyme inhibitor (ACEI), plasma levels of aldosterone have been shown to increase and this increase would blunt the effectiveness of the ACEI (aldosterone escape phenomenon). 2In the present study, we assessed a potential renal benefit of additional aldosterone blockade with spironolactone in hypertensive diabetic patients treated with ACEI showing the phase of aldosterone escape. 3The present clinical study was a randomized prospective study to assess difference between the clinical effects of spironolactone and furosemide. Thirty hypertensive type II diabetics (DM2) with a urinary alubumin : creatinine ratio (ACR) above 30 mg/g creatinine (showing albuminuria) and plasma B-type natriuretic peptide (BNP) levels above 100 pg/mL (showing mild heart failure) were treated with an ACEI (imidapril 5 mg/day) for 1 year and then randomly divided into two groups, one group receiving additional spironolactone (25 mg/day) treatment and the other receiving furosemide (20 mg/day) treatment. Blood pressure, ACR and plasma BNP levels were monitored in both groups. 4Treatment with the ACEI reduced ACR initially but, in 1 year, ACR tended to increase. Additional spironolactone treatment progressively reduced ACR, whereas furosemide treatment did not show any effect. Plasma BNP levels were reduced by ACEI and were further reduced by additional spironolactone treatment, but not furosemide treatment. Blood pressure levels in both groups were comparable. 5In conclusion, additional therapy with spironolactone in ACEI treatment exerts a renoprotective, as well as cardioprotective, effect in hypertensive diabetes. [source] ACUTE KIDNEY INJURY COMPLICATING MINIMAL CHANGE DISEASE: THE CASE FOR CAREFUL USE OF DIURETICS AND ANGIOTENSIN-CONVERTING ENZYME INHIBITORSNEPHROLOGY, Issue 5 2007RAJESH YALAVARTHY [source] Can an Angiotensin Receptor Blocker Be Used in a Patient in Whom Angioedema Developed With an Angiotensin-Converting Enzyme Inhibitor?JOURNAL OF CLINICAL HYPERTENSION, Issue 12 2008Debbie L. Cohen MD No abstract is available for this article. [source] What Should the Physician Do When Creatinine Increases After Starting an Angiotensin-Converting Enzyme Inhibitor or an Angiotensin Receptor Blocker?JOURNAL OF CLINICAL HYPERTENSION, Issue 10 2008Debbie L. Cohen MD No abstract is available for this article. [source] Pharmacological and Clinical Studies with Temocapril, an Angiotensin Converting Enzyme Inhibitor that is Excreted in the BileCARDIOVASCULAR THERAPEUTICS, Issue 3 2004Kenichi Yasunari ABSTRACT Temocapril is an angiotensin converting enzyme inhibitor (ACEI), a prodrug with a thiazepine ring. Its active form, temocaprilat, is slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of temocaprilat on isolated rat aorta is 3 times that of enalaprilat. Temocapril is excreted in the bile and urine and can be used in patients with renal insufficiency. It reduces blood pressure without causing any significant change in heart rate or cardiac output. Temocapril has been reported to improve endothelial dysfunction in vitro by suppressing increased oxidative stress. In vivo it improves reactive hyperemia in patients with essential hypertension. It has been reported to prevent coronary vascular remodeling in vivo by suppressing local ACE and increased oxidative stress. In humans temocapril has been found to improve insulin resistance partly by increasing adiponectin levels. Cardiac remodeling was improved by temocapril not only in experiment animals but also in humans. It improves renal function and decreases urinary albumin excretion in diabetics as well as in hypertensive patients. Temocapril is currently marketed only in Japan. Considering its beneficial effects and unique pharmaco-kinetics, temocapril, is likely to be introduced in other countries as well. [source] Elimination Mechanisms in the Aminolysis of Sulfamate Esters of the Type NH2SO2OC6H4X , Models of Enzyme InhibitorsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 24 2008William J. Spillane Abstract The kinetics of the reaction of 4-nitrophenyl sulfamate NH2SO2OC6H4NO2 -4 (1a) in acetonitrile (ACN) with a series of pyridines (pKa range ca. 8 units) and alicyclic amines (pKa range ca. 3.6 units) has been studied in the presence of excess amine at various temperatures. The compounds 1a,1f are important as model substrates for the medicinally important sulfamate esters 667-coumate and emate and analogues. Pseudo-first-order rate constants (kobsd.) have been obtained mainly by the release of 4-nitrophenol/4-nitrophenoxide. Slopes of plots of kobsd. vs. [amine] gave second-order rate constants (k2), and Brönsted plots were biphasic for the aminolysis (with alicyclic amines) with an initial slope ,1 = 0.53 and a subsequent slope ,2 = 0.19. The change in slope occurs near the first pKa of 1a (17.9) in ACN. Leaving-group effects were probed by using the same series of phenyl sulfamates, i.e. 1a,f and the alicyclic amines N -formylpiperazine and pyrrolidine. The reactions were considered to be dissociative in nature involving E2- and E1cB- type mechanisms with the phenyl sulfamate anion 2 being involved in pyridine and in the weaker alicyclic amines (,1 segment) and a phenyl sulfamate dianion 3 being involved with the stronger alicyclic bases (,2 segment). The calculation of Leffler indices (,) for bond-forming (base···H+) and bond-breaking (S,OAr) steps allows fuller interpretation of the mechanisms occurring, which are seen as having the N -sulfonylamines, HN=SO2 and ,N=SO2 on the reaction pathways leading to products. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Underutilization of Angiotensin-Converting Enzyme Inhibitors in High-Risk Blacks: A Case of Missed OpportunitiesJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2009Keith C. Ferdinand MD No abstract is available for this article. [source] Angiotensin-Converting Enzyme Inhibitors in the Treatment of Hypertension: An UpdateJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2007William B. White MD Angiotensin-converting enzyme inhibitors are an important treatment option for hypertension, especially when elevated blood pressure exists in the presence of diabetes mellitus, chronic kidney disease, or congestive heart failure. This article reviews some of the pathophysiologic mechanisms involved in patients with hypertension and these comorbidities and how they relate to the renin-angiotensin system (RAS). Inhibition of the RAS when utilized along with other antihypertensive medications has been particularly effective in hypertensive patients with type 2 diabetes, chronic kidney disease, and vascular disorders; consensus group guidelines have reflected this in their treatment recommendations. Clinical trial data demonstrate that the effectiveness of RAS blockers is enhanced by maximizing the daily dose and combining these medications with thiazide diuretics. [source] A Cost-Effectiveness Analysis of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Diabetic NephropathyJOURNAL OF CLINICAL HYPERTENSION, Issue 10 2007Panagiotis C. Stafylas MD The aim of this study was to estimate the cost-effectiveness of renin-angiotensin-aldosterone system blockers in patients with diabetic nephropathy. A cost-effectiveness analysis was performed based on a meta-analysis of studies investigating the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) as part of a treatment regimen on the incidence of end-stage renal disease (ESRD) in patients with diabetic nephropathy. The primary outcome was the cost to prevent 1 patient from developing ESRD. Cost analysis was performed from a third-party payer perspective in 2006 US dollars. As part of a treatment regimen, ARBs significantly reduced the incidence of ESRD and doubling of serum creatinine concentration (P<.05) but not total mortality. The cost to prevent 1 patient from developing ESRD was $31,729 (95% confidence interval, $19,443,$85,442; P<.01), $189,190 (P=.13) and $51,585 (P=.068) for patients receiving ARBs, ACE inhibitors, or either of them, respectively. This study demonstrates that blocking the RAAS, which delays the progression to ESRD, appears to be cost-effective. The current analysis favors ARBs in terms of cost-effectiveness. [source] Cardiovascular Events in Hypertension Trials of Angiotensin-Converting Enzyme InhibitorsJOURNAL OF CLINICAL HYPERTENSION, Issue 2005William J. Elliott MD Angiotensin-converting enzyme inhibitors are widely-prescribed drugs for hypertension and are supported by clinical trials in which they reduce cardiovascular events. In the high-risk patients in the Heart Outcomes Prevention Evaluation, the Perindopril Protection Against Recurrent Stroke Study, and European Trial of Reduction of Cardiac Events With Perindopril in Stable Coronary Artery Disease, ramipril and perindopril showed impressive benefits. One reason trandolapril did somewhat less well in the Prevention of Events With Angiotensin-Converting Enzyme Inhibition trial may be that its patients were very well treated with other effective modalities. In the Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial, lisinopril-treated patients had a slightly lower incidence of myocardial infarction, despite much poorer control of blood pressure, perhaps because a second-line diuretic was prohibited by protocol. Although angiotensin-converting enzyme inhibitors can cause cough and angioedema (more common among blacks), angiotensin receptor blockers are currently more expensive and have fewer outcome trials to support their use. [source] The Effect of Angiotensin-Converting Enzyme Inhibitors of Left Atrial Pressure in Dogs with Mitral Valve RegurgitationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2010T. Ishikawa Background: Despite many epidemiological reports concerning the efficacy of angiotensin-converting enzyme (ACE) inhibitors in dogs with mitral regurgitation (MR), the hemodynamic effects of ACE inhibitor administration have not been fully evaluated. Objectives: To document left atrial pressure (LAP) in dogs with MR administered ACE inhibitors, in order to obtain interesting information about daily LAP changes with administration of ACE inhibitors. Animals: Five healthy Beagle dogs weighing 9.8 to 14.2 kg (2 males and 3 females; aged 2 years). Methods: Experimental, crossover, and interventional study. Chordae tendineae rupture was induced, and a radiotelemetry transmitter catheter was inserted into the left atrium. LAP was recorded for 72 consecutive hours during which each of 3 ACE inhibitors,enalapril (0.5 mg/kg/d), temocapril (0.1 mg/kg/d), and alacepril (3.0 mg/kg/d),were administered in a crossover study. Results: Averaged diurnal LAP was significantly, but slightly reduced by alacepril (P= .03, 19.03 ± 3.01,18.24 ± 3.07 mmHg). The nightly drops in LAP caused by alacepril and enalapril were significantly higher than the daily drops (P= .03, ,0.98 ± 0.19 to ,0.07 ± 0.25 mmHg, and P= .03, ,0.54 ± 0.21,0.02 ± 0.17 mmHg, respectively), despite the fact that the oral administrations were given in the morning. Systolic blood pressure (122.7 ± 14.4,117.4 ± 13.1 mmHg, P= .04) and systemic vascular resistance (5800 ± 2685,5144 ± 2077 dyne × s/cm5, P= .03) were decreased by ACE inhibitors. Conclusions and Clinical Importance: ACE inhibitors decrease LAP minimally, despite reductions in left ventricular afterload. ACE inhibitors should not be used to decrease LAP. [source] Titelbild: In Situ Assembly and Screening of Enzyme Inhibitors with Surface-Tension Microarrays (Angew. Chem.ANGEWANDTE CHEMIE, Issue 41 200941/2009) Die Bildung von Regentropfen auf einer Blattoberfläche spiegelt eine wesentliche Eigenschaft von Wasser wider: die hohe Oberflächenspannung. Eine künstliche Anordnung sehr einheitlicher Tropfen lässt sich auf einer lithographisch bemusterten Glasoberfläche mit einer differenziellen Oberflächenenergie erzeugen. M.,Y. Balakirev et,al. schildern in der Zuschrift auf S.,7775,ff. die Verwendung dieser Tropfen für die Synthese kleiner Moleküle in Lösung und die anschließende quantitative Hochdurchsatzanalyse der Enzymkinetik. [source] In Situ Assembly and Screening of Enzyme Inhibitors with Surface-Tension Microarrays,ANGEWANDTE CHEMIE, Issue 41 2009Laurent Mugherli Dr. Hunderte von Reaktionen wurden bei einer neuartigen Synthese im Submikroliter-Maßstab parallel in Tropfen durchgeführt, die durch differenzielle Oberflächenspannung auf einem Glasträger gehalten wurden. Dieser ,Oberflächenspannungs-Mikroarray" wurde genutzt, um Tausende von Phenylboronsäurederivaten aufzubauen und gegen die NS3/4A-Protease des Hepatitis-C-Virus zu testen. Mehrere hochwirksame Inhibitoren des Enzyms wurden identifiziert. [source] The Effects of Angiotensin Converting Enzyme Inhibitors on Potassium Homeostasis in Dialysis Patients With and Without Residual Renal FunctionARTIFICIAL ORGANS, Issue 8 2009Elizabeth Garthwaite Abstract Hyperkalemia is exacerbated by angiotensin converting enzyme inhibitors (ACE-I). Distal potassium (K+) secretion is negligible in anuric patients. ACE-I therapy may reduce renal, peritoneal, and colonic K+ losses. We examined the effect of ACE-I therapy on serum, urinary, and dialysate K+ in a cross-section of peritoneal and hemodialysis patients. Serum, 24-h urine K+, and peritoneal dialysate excretion K+ levels were measured and the results were compared in the various dialysis and treatment groups. Eighty-one hemodialysis (HD) and 32 peritoneal dialysis (PD) patients were included. Serum K+ in HD patients with no residual renal function (RRF) was higher in those receiving ACE-I therapy (P = 0.02). Serum K+ levels in HD patients receiving ACE-I treatments with RRF was similar to that in oligoanuric HD patients not receiving an ACE-I. Urinary K+ excretion was significantly reduced in those on ACE-I therapy versus those not on an ACE-I (P < 0.05). Mean serum K+ was lower in PD versus HD patients (P < 0.05). PD patients with no RRF on ACE-I therapy had higher serum K+ concentrations (P = 0.002) and dialysate K+ excretion was lower (P = 0.05), in comparison with PD patients not on an ACE-I. PD patients with RRF on ACE-I therapy had higher serum K+ concentrations compared with those not on ACE-I therapy (P = 0.03). Both urinary and dialysate K+ excretion were reduced (P = 0.001 and P = 0.002, respectively). ACE-I therapy increases serum K+ concentration in dialysis patients. PD patients have relatively lower serum K+ levels compared with HD patients. In PD patients, ACE-I therapy reduces dialysate K+. These changes may result from reduced peritoneal movement of K+. [source] Management Strategies for Stage-D Patients with Acute Heart FailureCLINICAL CARDIOLOGY, Issue 7 2008David Feldman M.D., Ph.D. Abstract Heart Failure (HF) accounted for 3.4 million ambulatory visits in 2000. Current guidelines from the American Heart Association/American College of Cardiology, the Heart Failure Society of America, and the International Society for Heart & Lung Transplantation recommend aggressive pharmacologic interventions for patients with HF. This may include a combination of diuretics, Angiotensin Converting Enzyme inhibitors, ,-blockers, angiotensin receptor blockers, aldosterone antagonists, and digoxin. Nitrates and hydralazine are also indicated as part of standard therapy in addition to ,-blockers and Angiotensin Converting Enzyme inhibitors, especially but not exclusively, for African Americans with left ventricular (LV) systolic dysfunction. For those with acute decompensated HF, additional treatment options include recombinant human B-type natriuretic peptide, and in the future possible newer agents not yet approved for use in the U.S., such as Levosimendan. Medical devices for use in patients with advanced HF include LV assist devices, cardiac resynchronization therapy, and implantable cardioverter defibrillators. For refractory patients, heart transplantation, the gold-standard surgical intervention for the treatment of refractory HF, may be considered. Newer surgical options such as surgical ventricular restoration may be considered in select patients. Copyright © 2007 Wiley Periodicals, Inc. [source] Prognosis and Mechanism of Death in Treated Heart Failure: Data From the Placebo Arm of Val-HeFTCONGESTIVE HEART FAILURE, Issue 3 2006Jay N. Cohn MD The magnitude of benefit on mortality of combined angiotensin-converting enzyme inhibitor (ACEI) and ,-blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent-to-treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val-HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow-up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure-related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year. [source] HOPE for patients with Type 2 diabetes: an application of the findings of the MICRO-HOPE substudy in a British hospital diabetes clinicDIABETIC MEDICINE, Issue 8 2001S. C. Jones Abstract Aims, The MICRO-HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service. Methods, Non-proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO-HOPE substudy. Results, Non-proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty-nine percent were already taking an angiotensin-converting enzyme inhibitor. The remaining 764 patients were similar to ramipril-treated participants in the MICRO-HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively. Conclusions, Of non-proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin-converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed. Diabet. Med. 18, 667,670 (2001) [source] An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54)DIABETIC MEDICINE, Issue 6 2001A. Gray Abstract Aims To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or , blocker (atenolol) in patients with Type 2 diabetes. Design A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. Setting Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. Subjects Hypertensive patients (n= 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the , blocker atenolol. Main outcome measures Life expectancy and mean cost per patient. Results There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was £6485 in the captopril group, compared with £5550 in the atenolol group, an average cost difference of £935 (95% confidence interval £188, £1682). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. Conclusions Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438,444 (2001) [source] Effect of Losartan on Sodium Appetite of Hypothyroid Rats Subjected to Water and Sodium Depletion and Water, Sodium and Food DeprivationEXPERIMENTAL PHYSIOLOGY, Issue 5 2001D. Badauê-Passos Jr The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg g,1, the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg g,1 did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors. [source] Perindopril protection against recurrent stroke study: An overview of published resultsGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2005Matthew Walters The Perindopril Protection Against Recurrent Stroke Study was designed to clarify the role of intervention to lower blood pressure after stroke. Its aim was to determine the effect of long-term treatment with an angiotensin converting enzyme inhibitor-based blood pressure lowering regimen in patients with a history of non-disabling stroke. A series of publications have reported the design and both main and subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study trial. This article will provide an overview of the trial and draw together the results of previously-published primary, secondary and subgroup analyses. [source] Some properties of polyphenol oxidase from lilyINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 1 2008Ying Yang Summary A study of crude polyphenol oxidase (PPO) from lily bulbs was carried out to provide information useful for guiding food processing operations. Optimum pH for the enzyme activity in the presence of catechol, were 4.0 and 7.0 at room temperature(approximately 20 °C) and the enzyme was stable in the pH range from 5.0 to 6.5 at 4 °C for 10 h. Its optimum temperature was 40 °C and the heat inactivation of the enzyme followed first-order kinetics. Lily PPO possessed a diphenolase activity toward catechol, catechin and gallic acid; catechin was the best substrate for the enzyme considering the Vmax/Km ratio. The most effective enzyme inhibitor was sodium sulphite, although ascorbic acid, l -cysteine and thiourea were also effective inhibitors at high concentration. But NaCl and citric acid were poor inhibitors of the enzyme. Data generated by this study might help to better prevent lily bulbs browning. [source] Beneficial effect of enalapril in spontaneously hypertensive rats cardiac remodeling with nitric oxide synthesis blockadeJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2002R. L. de Andrade Zorzi Abstract Aims. To study the efficiency of an angiotensin converting enzyme inhibitor on the blood pressure (BP) and the myocardium remodeling when spontaneously hypertensive rats (SHRs) are submitted to nitric oxide synthesis (NOs) blockade (with L-NAME) and simultaneously treated. Methods. Young adult male SHRs were separated in four groups (n = 5) and treated for 20 days: Control, L-NAME, L-NAME+Enalapril, and Enalapril. The alterations of the BP, heart mass/body mass ratio and stereological parameters for myocytes, connective tissue and intramyocardial vessels were studied among the groups. Results. The SHRs with NOs blockade showed a great modification of the myocardium with extensive areas of reparative and interstitial fibrosis and accentuated hypertrophy of the cardiac myocytes (cross sectional area 60% higher in animals taking L-NAME than in Control SHRs). Comparing the SHRs with NO deficiency (L-NAME group), the Control SHRs and the Enalapril treated SHRs significant differences were found in the BP and in all stereological parameters. The NO deficiency caused an important BP increment in SHRs that was partially attenuated by Enalapril. This Enalapril effect was more pronounced in Control SHRs. A significant increment of the intramyocardial vessels was observed in NO deficient SHRs and Control SHRs treated with Enalapril demonstrated by the stereology (greater microvascular densities in treated SHRs). Conclusion. Enalapril administration showed a beneficial effect on vascular remodeling and myocardial hypertrophy in SHRs. In SHRs with NO blockade, however, the beneficial effect of Enalapril occurred only in vascular remodeling. [source] Emerging Insights in the First-Step Use of Antihypertensive Combination TherapyJOURNAL OF CLINICAL HYPERTENSION, Issue 2007Keith Norris MD The blood pressure (BP) goals set by hypertension management guidelines (<140/90 mm Hg in uncomplicated hypertension; <130/80 mm Hg in type 2 diabetes or kidney disease) are not being achieved in a high proportion of patients, partly because monotherapy is insufficient in many patients. In particular, patients with uncontrolled moderate or severe hypertension and/or associated cardiovascular risk factors remain at high risk for cardiovascular events and hypertensive emergency. In recognition of the urgency of treating moderate and severe hypertension, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) advocates the initial use of 2-drug therapies in patients with systolic BP levels >20 mm Hg above goal or diastolic BP level >10 mm Hg above goal. Regimens should usually include a thiazide diuretic and, for patients with diabetes or kidney disease, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Recently, clinical trial data have shown that first-step antihypertensive treatment of moderate and severe hypertension with carefully chosen fixed-dose combinations provides a high rate of BP goal achievement, a simplified dosing regimen, and superior tolerability compared with monotherapy. [source] Your Drug, My Drug, or Our Drugs: How Aggressive Should We Be With Antihypertensive Therapy?JOURNAL OF CLINICAL HYPERTENSION, Issue 2005Joseph L. Izzo Jr. MD In the prevention of hypertensive complications, especially stroke and kidney disease, "lower is better" because for each decrease of 20 mm Hg systolic or 10 mm Hg diastolic pressure in the population, cardiovascular risk is halved. Ideally, the goal for each patient should be to reach the lowest blood pressure that is well tolerated, a value that may be well below the arbitrary threshold value of 140/90 mm Hg. For the majority of "uncomplicated hypertensives," the question of single-drug therapy is essentially moot, because more than one agent is almost always required to optimally control blood pressure. In individuals who already have heart or kidney disease, there are compelling indications for the use of drugs that block the renin-angiotensin system, but the large outcome studies that spawned these recommendations are themselves combination trials. Thus, in virtually all patients, more than one drug is indicated. The best combinations take advantage of long durations of action and complementary mechanisms of action of the component and are not only able to effectively lower blood pressure, but also to favorably affect the natural history of hypertensive complications. Regimens,including fixed-dose combination products,that combine a thiazide diuretic or calcium antagonist with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker are most efficient. In summary, why would an astute clinician (or informed patient) be satisfied with the relatively limited effects of any single class of antihypertensive agents when better overall protection is possible? [source] Update on the Management of Hypertension: Recent Clinical Trials and the JNC 7JOURNAL OF CLINICAL HYPERTENSION, Issue 2004Marvin Moser MD Editor in Chief The following issues are highlighted: Emphasis is placed on the importance of systolic blood pressure elevations in estimating risk and in determining prognosis. A review of placebo-controlled clinical trials indicates that cardiovascular events are statistically significantly reduced with diuretic- or , blocker-based treatment regimens. The question of whether blood pressure lowering alone or specific medications make the difference in outcome is discussed. Based on the results of numerous trials, it is apparent that blood pressure lowering itself is probably of greater importance in reducing cardiovascular events than the specific medication used. Meta-analyses suggest, however, that the use of an agent that blocks the renin-angiotensin aldosterone system is probably more effective in diabetics and in patients with nephropathy than a regimen based on calcium channel blocker therapy. The Antihypertensive and Lipid-Lowering treatment to Prevent Heart Attack Trial (ALLHAT) reported no overall difference in coronary heart disease outcome among patients treated with a diuretic-based compared to a calcium channel blocker- or an angiotensin-converting enzyme inhibitor-based treatment program. However, patients in the diuretic group experienced fewer episodes of heart failure than in the calcium channel blocker group and fewer episodes of heart failure and strokes than those in the angiotensin-converting enzyme inhibitor group. Results were similar in diabetics and nondiabetics. Possible reasons for this outcome are discussed. The Australian National Blood Pressure 2 study, which was unblinded, reported a marginally significantly better outcome only in male patients receiving an angiotensin-converting enzyme inhibitor-based regimen compared to those receiving a diuretic-based program. Finally, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is reviewed. Highlights of this report include the new designation of prehypertension, i.e., blood pressures of 120,139 mm Hg/80,89 mm Hg. The JNC 7 suggested that diuretics should be the first-step drug of choice in most patients, but listed numerous specific reasons why other agents should be used in special situations. The report stressed that the majority of patients will require two or more medications to achieve goal blood pressure. [source] Meeting the Challenge to Improve the Treatment of Hypertension in BlacksJOURNAL OF CLINICAL HYPERTENSION, Issue 6 2003Antonio Alberto Lopes MD Hypertension is more prevalent and severe in African descendent populations living outside Africa than in any other population. Given this greater burden of hypertension in blacks, it is increasingly necessary to refine strategies to prevent the disorder as well as improve its treatment and control. This review assesses results from clinical trials on lifestyle and pharmacologic interventions to identify which approaches most effectively prevent adverse hypertension-related outcomes in African descendent populations. The Dietary Approaches to Stop Hypertension (DASH) study provided evidence that a carefully controlled diet rich in fruits, vegetables, low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (i.e., the DASH diet) reduces blood pressure in blacks and is well accepted. The combination of the DASH diet with reduction in dietary sodium below 100 mmol/d may provide a reduction in blood pressure beyond that reached by the DASH diet alone. Physical exercise and interventions to reduce psychological stress may also reduce blood pressure in blacks. Strong evidence from numerous studies is a compelling argument for continuing to recommend diuretics and , blockers as first-line antihypertensive therapy for persons of all races. Some new studies also favor angiotensin-converting enzyme inhibitors as first-line antihypertensive drugs. The African American Study of Kidney Disease and Hypertension provided evidence that an angiotensin-converting enzyme inhibitor-based treatment program is more beneficial than calcium channel blockers and , blockers in reducing the progression of renal failure in blacks with hypertensive nephropathy. Studies in patients with diabetes have also shown evidence that both angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists are more effective than other classes of antihypertensives in reducing adverse renal events. Studies to evaluate the effects of the new antihypertensives in improving outcomes in blacks living outside the United States are needed. [source] Calcium Channel Blocker-Related Peripheral Edema: Can It Be Resolved?JOURNAL OF CLINICAL HYPERTENSION, Issue 4 2003Domenic A. Sica MD Calcium channel blocker (CCB)-related edema is quite common in clinical practice and can effectively deter a clinician from continued prescription of these drugs. Its etiology relates to a decrease in arteriolar resistance that goes unmatched in the venous circulation. This disproportionate change in resistance increases hydrostatic pressures in the precapillary circulation and permits fluid shifts into the interstitial compartment. CCB-related edema is more common in women and relates to upright posture, age, and the choice and dose of the CCB. Once present it can be slow to resolve without intervention. A number of strategies exist to treat CCB-related edema, including switching CCB classes, reducing the dosage, and/or adding a known venodilator such as a nitrate, an angiotensin-converting enzyme inhibitor, or an angiotensin-receptor blocker to the treatment regimen. Angiotensin-converting enzyme inhibitors have been best studied in this regard. Diuretics may alter the edema state somewhat, but at the expense of further reducing plasma volume. Traditional measures such as limiting the amount of time that a patient is upright and/or considering use of graduated compression stockings are useful adjunctive therapies. Discontinuing the CCB and switching to an alternative antihypertensive therapy will resolve the edema. [source] Browning Prevention by Ascorbic Acid and 4-Hexylresorcinol: Different Mechanisms of Action on Polyphenol Oxidase in the Presence and in the Absence of SubstratesJOURNAL OF FOOD SCIENCE, Issue 9 2007E. Arias ABSTRACT:, We have investigated the mechanism of action of 4-hexylresorcinol (4-HR) and ascorbic acid (AA) on the polyphenol oxidase (PPO) catalyzed oxidation of phenolic substrates. Incubation of PPO with 4-HR diminishes strongly PPO activity. This effect can be erroneously interpreted, due to the high affinity of 4-HR for PPO, as irreversible inactivation of PPO. However, PPO activity can be recovered by dialysis after incubation with 4-HR. 4-hexylresorcinol is a canonical enzyme inhibitor that binds preferentially to the oxy form of PPO. It is a mixed-type inhibitor, because it influences both apparent Vmax (1.26 compared with 0.4 units in the absence and presence of 4-HR, respectively) and Km values (0.28 mM compared with 0.97 mM in the absence and in the presence of 4-HR, respectively) of PPO. AA can prevent browning by 2 different mechanisms: In the absence of PPO substrates it inactivates PPO irreversibly, probably through binding to its active site, preferentially in its oxy form. In the presence of PPO substrates, AA reduces PPO oxidized reaction products, which results in a lag phase when measuring PPO activity by monitoring dark product formation but not when monitoring O2 consumption. The simultaneous use of both 4-HR and AA on PPO results in additive prevention of browning. [source] Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in ratsJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Marcello Solinas Abstract Although endogenous cannabinoid systems have been implicated in the modulation of the rewarding effects of abused drugs and food, little is known about the direct effects of endogenous ligands for cannabinoid receptors on brain reward processes. Here we show for the first time that the intravenous administration of anandamide, an endogenous ligand for cannabinoid receptors, and its longer-lasting synthetic analog methanandamide, increase the extracellular dopamine levels in the nucleus accumbens shell of awake, freely moving rats, an effect characteristic of most drugs abused by humans. Anandamide produced two distinctly different effects on dopamine levels: (1) a rapid, transient increase that was blocked by the cannabinoid CB1 receptor antagonist rimonabant, but not by the vanilloid VR1 receptor antagonist capsazepine, and was magnified and prolonged by the fatty acid amide hydrolase (FAAH) enzyme inhibitor, URB597; (2) a smaller delayed and long-lasting increase, not sensitive to CB1, VR1 or FAAH blockade. Both effects were blocked by infusing either tetrodotoxin (TTX, 1 µm) or calcium-free Ringer's solution through the microdialysis probe, demonstrating that they were dependent on the physiologic activation of dopaminergic neurotransmission. Thus, these results indicate that anandamide, through the activation of the mesolimbic dopaminergic system, participates in the signaling of brain reward processes. [source] Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve DiseaseJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2010F. Bernay Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double-blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac-related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22,0.90; log rank test, P= .017). Risk of cardiac- related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13,0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD. [source] | ||||||||||||||||||||||||||||||||||||||||