bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of ACE inhibition and AT1-receptor blockade on haemodynamic responses to L-arginine in Type 1 diabetes
Authors: Komers Radko , Simkova Renata , Kazdova Ludmila , Ruzickova Jana , Pelikanova Terezie 
Published: May 2007

Introduction Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve endothelial function in Type 1 diabetes. However, the potential of ACE inhibitors (ACE-I) to enhance the haemodynamic effects of L-arginine (L-arg), the precursor of nitric oxide (NO), has not been evaluated. Furthermore, angiotensin receptor blockers (ARBs), another group of inhibitors of the renin-angiotensin system (RAS), have not been studied in this context. Methods Using a randomised, crossover design, the acute effects of L-arg (200 mg/kg) on blood pressure (BP) and renal haemodynamics were determined in uncomplicated Type 1 diabetic patients before and after three weeks of treatment with the ACE-I ramipril (5 mg/day) or the ARB losartan (50 mg/day). Results L-arg alone did not influence BP or renal haemodynamics. BP responses to L-arg were not modulated by ACE-I or ARB. In contrast to the systemic responses, L-arg induced significant renal vasodilation after treatment with ramipril (p<0.05). Unlike ramipril, losartan did not modulate renal haemodynamic responses to L-arg. L-arg administration was paralleled by increments in plasma L-citrulline levels, determined as a measure of L-arg-induced systemic NO production. These responses were not influenced by RAS inhibitors. No changes in other indicators of the systemic and renal NO production, such as plasma and urinary nitrates/nitrites, were detected in response to L-arg alone or after treatment with RAS inhibitors. Conclusions ACE-Is have greater potential than ARBs to enhance L-arg effects in the kidney in uncomplicated Type 1 diabetes. Neither RAS inhibitor influenced the systemic effects of L-arg. The lack of changes in renal NO indicators parallelling the haemodynamic responses, suggests that the effects of ACE-I on L-arg-induced renal haemodynamic changes could be also attributable to NO-independent mechanisms.
Regulation of renal proximal fluid uptake by luminal and peritubular angiotensin II
Authors: Hiranyachattada Siriphun , Harris Peter J 
Published: May 2007

Introduction Angiotensin II (Ang II), when administered to either tubular lumen or peritubular capillary, exerts a biphasic action on proximal fluid uptake rate. At low concentrations, (10-12—10-10M) Ang II stimulates fluid transport, whereas higher doses (> 10-9 M) inhibit. Ang II is secreted into the lumen in the proximal tubule and the concentration of Ang II in the proximal lumen has been reported to be in the nanomolar range, 100—1,000 times higher than in peritubular blood. We investigated the regulation of renal proximal fluid transport by luminal (predominantly locally produced) and peritubular capillary (circulatory) Ang II in anaesthetised rats, using a selective AT1-receptor antagonist, candesartan.
BNP and ANP as diagnostic and predictive markers in heart failure with left ventricular systolic dysfunction
Authors: Menezes Falcão Luiz , Pinto Fausto , Ravara Luciano , van Zwieten Peter Adriaan 
Published: May 2007

Background The prevalence of chronic heart failure (CHF) with systolic dysfunction is increasing. Plasma natriuretic peptides have been envisaged as diagnostic and predictive markers. Aims To investigate the relationship between the levels of B-type natriuretic peptide (BNP) and A-type natriuretic peptide (ANP) and the clinical and functional parameters of CHF in outpatients with CHF at baseline, compared with normal healthy controls; to find out the differences in a randomised controlled trial between patients treated with an angiotensin-converting enzyme (ACE) inhibitor, captopril, or an angiotensin receptor blocker (ARB), irbesartan. These differences were assessed throughout the six-month treatment period and at the sixth month. Methods Plasma BNP (pmol/L) and ANP (pmol/L) were determined in 68 hypertensive patients with dilated cardiomyopathy, NYHA class III-IV and ejection fraction (EF) <40%, and in 26 normal controls. Statistical analysis for BNP and ANP was done by Student's t-test. The patient group was randomly subdivided into two subgroups of 34 patients, each treated with either an ARB, irbesartan, or an ACE inhibitor (ACE-I), captopril. BNP and ANP were measured in both subsamples and correlated with clinical, functional and neurohormonal parameters throughout a follow-up period of six months and at the sixth month. Results The mean EF in the patient sample was 33.43±6.52% and in the controls was 61.96 ±3.53% (p=0.000). The mean BNP (pmol/L) in patients was 44.78±54.36 and in the controls was 7.12±8.28 (p=0.000) and the mean ANP (pmol/L) was 30.32±25.97 in patients and 11.18±7.92 in controls (p=0.000). A statistically significant difference was found between patients and healthy controls. Significant correlations were found between natriuretic peptides and EF. Between the baseline phase and the sixth month, BNP and ANP decreased significantly in the ARB group. At the sixth month, both BNP and ANP were lower in the ARB group. Evidence of clinical benefit was found with both ARB or ACE-I treatment throughout the six months, with patients moving from classes III and IV to class II NYHA. Improvement of EF was also found, with transition of patients with lower EF (even <30%) to higher values. EF was higher in the ARB group at the sixth month. Conclusions BNP and ANP can be useful diagnostic tools in hypertensive CHF patients with moderate-to-severe LV dysfunction. The decrease in BNP and ANP in the ARB group throughout six months, as well as the lower value at the sixth month, suggest a prognostic value of these parameters.
Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor β1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat
Authors: Erman Arie , Veksler Semyon , Gafter Uzi , Boner Geoffrey , Wittenberg Clara , van Dijk David Jonathan 
Published: May 2007

Introduction Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor β1 (TGF-β1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-β1 in diabetic rats. Materials and methods Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. Results Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-β1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-β1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). Conclusions Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-β1.
The VALUE trial: a commentary
Authors: Sever Peter 
Published: May 2007

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial compared coronary heart disease outcome in two anti-hypertensive treatment strategies based on either an angiotensin receptor blocker, valsartan, or a calcium channel blocker (CCB), amlodipine. In both patient groups a diuretic was added, if necessary, in an attempt to achieve blood pressure (BP) goals. Follow-up of over 15,000 patients was maintained for 4.2 years. There were no differences in the primary composite endpoint of cardiac morbidity and mortality (which included interventional procedures, hospitalised heart failure, non-fatal myocardial infarction and fatal coronary heart disease, however myocardial infarction and stroke events occurred less commonly on amlodipine than on valsartan — the former achieving statistical significance [p=0.02 and p=0.08 respectively]). There was a non-significant excess of hospitalised heart failure on amlodipine (p=0.012). However, lower BPs early in the trial probably accounted for most of the observed benefits in favour of the CCB. The angiotensin receptor blocker arm was associated with less new onset diabetes. The results of VALUE add further support to the evidence that blood pressure control is the major determinant in outcome in trials of antihypertensive therapy.
Renin-angiotensin system gene polymorphisms and premature coronary heart disease
Authors: Sekuri Cevad , Cam F Sirri , Ercan Ertugrul , Tengiz Istemihan , Sagcan Abdi , Eser Erhan , Berdeli Afig , Akin Mustafa 
Published: May 2007

Introduction Experimental and clinical studies demonstrated that the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and prognosis of coronary heart disease (CHD). The aim of this study was to investigate the genotype distribution and the allele frequencies of three RAS genes polymorphisms and their effects on premature CHD in a Turkish population. Materials and methods One-hundred and fifteen Turkish patients with premature CHD and 128 controls were included into the study. Angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor and angiotensinogen (AGT) gene polymorphisms were analysed by polymerase chain reaction (PCR ) and restriction fragment length polymorphism (RFLP). Results The patients group showed an increased frequency of the ACE D allele compared with controls (65% vs. 35%, p=0.0001). There was a significant association between the DD genotype and premature CHD (ACE DD vs. ID and II; odds ratio [OR]=2.82 [CI 95% 1.33—2.91, p=0.002]). Also, we observed increased premature CHD risk associated with higher frequencies of the AGT MM genotype in patients when compared with controls (AGT MM vs. TT and MT, OR=1.92 [CI 95% 1.11—3.33, p=0.018]). We found a significant association between AT1-receptor AA genotype and decreased risk of premature CHD (AT1R AA vs. AC and CC, OR= 0.57[CI 95% 0.34—0.95, p=0.03]). Conclusions We demonstrated that increased premature CHD risk is associated with higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a synergistic contribution of ACE DD and AGT MM polymorphisms to the development of premature CHD. Also, our results suggest that family history, smoking, diabetes, hypertension, obesity and ACE DD genotype were independent risk factors for premature CHD.
Collagen Production in Cardiac Fibroblasts During Inhibition of Aminopeptidase B
Authors: Lijnen Paul J , Petrov Victor V , Turner Marisa , Fagard Robert H 
Published: May 2007

Objective. To determine whether the aminopeptidase B inhibitor, arphamenine A, could affect collagen production and expression in control and TGF-ß1-treated cardiac fibroblasts. Design and Methods. Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency and incubated with and without 600 pmol/l TGF-ß1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with 100 µmol/l arphamenine A for 1 day in this medium added ascorbic acid, ß-aminopropionitrile and titriated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Matrix metalloproteinase (MMP) and lysyl oxidase activity were assayed in the conditioned medium. A semi-quantitative reverse transcriptase- polymerase chain reaction was used to examine the expression of lysyl oxidase and collagen type I and III. Results. Arphamenine A dose-dependently inhibited basal and TGF-ß 1-stimulated aminopeptidase activity. Arphamenine A reduced soluble and non-soluble collagen production in control and TGF-ß1-treated cardiac fibroblasts, while it decreased collagen type I and III expression only in TGF-ß1-treated fibroblasts. Lysyl oxidase, MMP-1 and MMP-2 activity were inhibited by arphamenine A in the conditioned media of control and TGF-ß1treated cardiac fibroblasts. Conclusions. Our data show that the specific aminopeptidase B inhibitor, arphamenine A, reduces collagen production in cardiac fibroblasts and that this reduction is accompanied by a pronounced inhibition of lysyl oxidase.
Renin Release in Response to Renin System Blockade: Activation of the Renin System in Type 1 Diabetes Mellitus
Authors: Stevanovic Radomir D , Price Deborah A , Lansang M Cecilia , Fisher Naomi DL , Laffel Lori MB , Hollenberg Norman K 
Published: May 2007

Activation of the renin-angiotensin system (RAS) in diabetes is thought to contribute to nephropathy. This is suggested by findings of an enhanced renovascular (RPF) response to RAS blockade with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). An alternative approach to assess RAS activation is the evaluation of renin release following RAS blockade. Forty-four consecutively enrolled Type 1 diabetic patients (28.2 ± 1.5 years) and 37 normal subjects (37 ± 2.6 years) in high salt balance were given 25 mg of captopril and 16 mg of candesartan p.o. on consecutive days. All subjects were Caucasian. All, except one diabetic patient, had normal renal function. Plasma renin activity (PRA) and renal plasma flow (RPF) were measured for four hours after both drugs, and at eight, and 24 hours after candesartan. As anticipated, both drugs increased PRA. Peak responses (90' after captopril) were 5.6 ± 1 ng/mL Ang I/hour in diabetic patients, and 1.7 ± 0.9 ng/mL Ang I/hour in normal subjects (p<0.001). Responses to both drugs were correlated in diabetic patients for PRA (r=0.623; p=0.001) and for RPF (r=0.9; p<0.001). When the PRA response to captopril was below the median, the RPF response was limited (22.1 ± 17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2 ± 13.9 ml/minute/1.73 m2; p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients.
Comparison of Monotherapy with Irbesartan 150 mg or Amlodipine 5 mg for Treatment of Mild-to-Moderate Hypertension
Authors: Neutel Joel M , Germino F Wilford , Smith David 
Published: May 2007

Objective. The primary objective of this study was to compare the antihypertensive efficacy of the angiotensin II receptor blocker irbesartan 150 mg and the calcium channel blocker amlodipine 5 mg in the treatment of patients with seated diastolic blood pressure (DBP) 95—110 mmHg. Design. Multicentre, randomised, double-blind, comparative pilot study. Methods. Subjects were 18—65 years of age, with DBP 95—110 mmHg, and of non-African American origin. Following a three-week, single-blind, placebo lead-in period, 181 subjects were randomised in a 1:1 ratio to receive once-daily irbesartan 150 mg (n=89) or amlodipine 5 mg (n=92) for four weeks. Trough (24±3 hours post-dosing) BP measurements were obtained at baseline and at Weeks 2 and 4 under standardised, controlled conditions. Response was defined as DBP <90 mmHg or a reductionfrom baseline of ≥10 mmHg. Results. After four weeks of treatment, the mean (±SE) decrease from baseline in DBP was 9.4±0.6 mmHg in the irbesartan group vs. 9.6±0.6 mmHg in the amlodipine group (p=0.806). The mean decrease from baseline in seated systolic BP was 12.2±1.0 mmHg in the irbesartan group vs. 12.0±1.0 mmHg in the amlodipine group (p=0.885). Overall, 62% of subjects in the irbesartan group and 63% in the amlodipine group had a response (p=0.609), and 54% and 56% of patients (p=0.596), respectively, had their DBP normalised (<90 mmHg). Adverse events were reported by 21.3% of patients receiving irbesartan and 20.7% receiving amlodipine. Conclusions. Irbesartan 150 mg demonstrated comparable efficacy to amlodipine 5 mg, thereby confirming its value as an antihypertensive treatment option in non-African American patients with DBP 95—110 mmHg.
High Angiotensin II Responsiveness is Associated with Decreased Endothelium-Dependent Relaxation in Human Arteries
Authors: Voors Adriaan A , van Geel Peter Paul , Buikema Hendrik , Oosterga Margreeth , van Veldhuisen Dirk J , van Gilst Wiek H 
Published: May 2007

Introduction. Animal studies demonstrated an interaction between angiotensin II (Ang II) responsiveness and endothelium-dependent relaxation (EDR). However, this relation has not been well described in humans. Therefore, we investigated the relation between Ang II responsiveness and EDR in isolated human arteries. Materials and Methods. Segments of the internal mammary artery (IMA) were harvested from 89 patients undergoing coronary bypass surgery. Rings of these segments were exposed in organ bath experiments to metacholine (ME; 10 nmol/L -0.1 mmol/L) after precontraction with phenylephrine (PE; 10 µmol/L), and secondly to increasing concentrations of Ang II (0.1 nmol/L —1 µmol/L). Results. Patients with the highest contraction to Ang II showed the lowest ME relaxation (r=0.312; p=0.003). Angiotensin-converting enzyme (ACE)-inhibition significantly increased Ang II sensitivity (p=0.03). This increase was accompanied by a tendency toward decreased EDR (p=0.07). The inverse relation between Ang responsiveness and endotheliumdependent relaxation could not be explained by an increased tissue or serum ACE-inhibition in patients with a higher endothelium-dependent relaxation. Conclusions. High Ang II responsiveness inversely correlates to EDR in IMA's of patients with established coronary artery disease. Short-term treatment with an ACE-inhibitor increased the response to Ang II, but had an adverse effect on EDR.
Beneficial Effect of Eplerenone on Cardiac Remodelling and Electrical Properties of the Failing Heart
Authors: De Mello Walmor C 
Published: May 2007

Introduction. The effect of chronic administration of eplerenone on cardiac remodelling and electrical properties was investigated in the failing heart of cardiomyopathic hamsters (TO-2) at five months of age. Materials and Methods. Two-month-old hamsters were treated with eplerenone (200 mg/kg/day) administered into the chow for a period of three months. Measurements of membrane potential were performed with intracellular microelectrodes connected to a high impedance DC amplifier. The thickness of the ventricular wall as well as the area of fibrosis were measured. To investigate the influence of eplerenone on the electrogenic sodium pump myocytes were isolated from the ventricle and the pump current density was whole cell clamp configuration. measured in voltage clamped cells using the whole cell clamp configuration Results. The results indicated that: 1) the width of the left and right ventricular wall was significantly reduced; 2) the heart weight/body weight ratio was decreased by 38±2.4% (n=24 P ) (p<0.05); 3) the fibrotic area in the left ventricle (LV) was reduced by 12.6±2% (n=25) (p<0.05); 4) the incidence of cardiac arrhythmias was decreased from 58±3.8% (n=20) in the control to 40±4.1% (n=20) (p<0.05) in animals treated with eplerenone. Moreover, a significant reduction in the dispersion of the QT interval was found with the drug; 5) eplerenone increased the resting potential of ventricular fibres from 64.3±1.5 mV to 73.4±1.4 mV (n=30) (p<0.05), an effect related to the activation of an electrogenic sodium pump. The conduction velocity, in longitudinal direction, was enhanced from 50±2.2 cm/s (n=10) in the controls to 59±2.4 cm/s (n=13) (p<0.05) in animals treated with eplerenone. Conclusions. Eplerenone reduces cardiac remodelling, the incidence of cardiac arrhythmias and improves impulse propagation, an effect in part related to the antifibrotic effect of the drug but also to the activation of the electrogenic sodium pump.
Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST) Trial
Authors: Ruilope Luis M , Zanchetti Alberto 
Published: May 2007

Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP) goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS) blocker and a diuretic are widely used in combination. Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST) trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily (o.d.), or with amlodipine monotherapy (10 mg o.d.). Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and pro-inflammatory markers than amlodipine alone.
Effects of the PPAR-γ Agonist Rosiglitazone on Renal Haemodynamics and the Renin-Angiotensin System in Diabetes
Authors: Lansang M Cecilia , Coletti Caroline , Ahmed Sofia , Gordon Michael S , Hollenberg Norman K 
Published: May 2007

Background. Thiazolidinediones (TZD) have been reported to improve early stages of diabetic nephropathy independent of glycaemic control. Since blockade of the renin-angiotensin system (RAS) is known to reduce the risk of nephropathy, we hypothesised that the renal effect of TZDs might be related to a favourable effect on the intrarenal RAS. We aimed to determine if the TZD rosiglitazone could reduce RAS activation. Methods. We studied adult type 2 diabetic patients and placed them on rosiglitazone for three months. We have previously used the renal haemodynamic response to angiotensin-converting enzyme (ACE) inhibition to demonstrate the state of RAS activation, and thus measured renal plasma flow (RPF) and glomerular filtration rate (GFR) before and after administration of captopril at 0 month and at three months. Plasma renin activity (PRA), active renin, aldosterone and natriuretic peptides were analysed. Results. The RPF response to ACE inhibition was not altered.There was no change in GFR, PRA, active renin and aldosterone levels. Two patients developed oedema — one had an elevated baseline active renin and another had an elevated baseline aldosterone level. Conclusion. The favourable effects of TZDs on diabetic nephropathy is likely not related to an influence on the RAS.