bluuebunny/crossref_metadata_2025_split huggingface dataset:
High plasma adrenomedullin concentrations in patients with high-renin essential hypertension
Authors: Letizia Claudio , Subioli Stefano , Cerci Sabrine , Caliumi Chiara , Verrelli Cristiana , Delfini Enrica , Celi Massimiliano , Scuro Luigi , D'Erasmo Emilio 
Published: May 2007

Adrenomedullin (AM) is a novel peptide, first isolated from human phaeochromocytoma, which elicits a long-lasting vasorelaxant activity. Recently, it has been reported that endothelial cells produce AM and that immunoreactive AM plasma levels may be elevated in human arterial hypertension, although the exact pathophysiological role of AM remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system (RAAS) and plasma AM levels in patients with low-, medium- or high-renin essential hypertension. The study groups included 10 patients with low-renin essential hypertension (average age 42 15 years), nine patients with medium-renin essential hypertension (46 13 years), 11 patients with high-renin essential hypertension (42 14 years) and 12 healthy subjects (43 11 years). Our results demonstrated that the mean AM values of all patients with essential hypertension were 10.85 3.14 pg/ml; there was a statistical correlation (r=0.705; p<0.001) between plasma renin activity (PRA) and AM levels in hypertensives. In patients with high-renin essential hypertension, plasma AM levels (14.2 2.2 pg/ml) were significantly higher (p<0.001) than those of healthy subjects (8.7 2.1 pg/ml), patients with medium-renin essential hypertension (8.5 1.4 pg/ml), and patients with low-renin essential hypertension (9.1 1.5 pg/ml). There was no statistical difference in AM concentrations between medium- and low-renin hypertensive patients. In conclusion, we have found that, in hypertensive patients, plasma AM levels were increased only in high-renin individuals, suggesting a role of AM in this particular form of human essential hypertension.
Involvement of the AT2-receptor in angiotensin II-induced facilitation of sympathetic neurotransmission
Authors: Balt Jippe C , Mathy Marie-Jeanne , Nap Alex , Pfaffendorf Martin , van Zwieten Pieter A 
Published: May 2007

Angiotensin II (Ang II) causes facilitation of sympathetic neurotransmission via prejunctionallylocated AT1-receptors. The pithed rat is a suitable model to study the interactions between endogenously produced Ang II and the sympathetic nervous system at the peripheral level. Previously, we demonstrated that inhibition of the facilitatory actions of Ang II is a class effect of all AT1-receptor blockers (ARB). However, all ARBs caused less than maximal inhibition after the highest dose, thus causing a U-shaped dose-response curve with respect to sympatho-inhibition. In the present study, we investigated whether the AT2-receptor is involved in this `upturn' of the dose-response relationship. Accordingly, we studied the effect of the ARB, irbesartan (1—60 mg/kg), on the sequelae of electric stimulation of the thoraco-lumbar sympathetic outflow in the presence and absence of the AT2blocker, PD 123319 (0.5 mg/kg +50 µg/kg/min). Additionally, the effect of the combined (non-selective) AT1/AT2-receptor antagonist saralasin (0.001, 0.003, 0.01 or 0.03 mg/kg/min), on stimulation-induced responses was studied. In addition, we measured PRA-levels after administration of irbesartan, in this model.The stimulation-induced increase in diastolic blood pressure (DBP) could be dose-dependently reduced by irbesartan. Co-infusion with PD 123319 increased the sympatho-inhibitory potency of irbesartan, possibly through displacement of irbesartan from plasma protein binding sites. The U-shaped dose-response relationship observed with irbesartan, which is illustrative for other ARBs in this model, was not observed when PD 123319 was co-administered with irbesartan, nor with the non-selective AT1/AT2blocker, saralasin. PRA-levels increased from 111.0±17.8 to 198.7±22.2 ng/ml/hour after administration of irbesartan. PRA-levels did not differ when measured after the three highest doses of irbesartan.Conclusions The present findings indicate a facilitatory role for the AT2-receptor, which is unmasked by the highest dose of irbesartan. Different plasma Ang II-levels are unlikely to have caused the less than maximal inhibition after the highest dose of irbesartan.
Comparative effects of aspirin with ACE inhibitor or angiotensin receptor blocker on myocardial infarction and vascular function
Authors: Zhu Bo-qing , Sievers Richard E , Browne Amanda EM , Lee Randall J , Chatterjee Kanu , Grossman William , Karliner Joel S , Parmley William W 
Published: May 2007

Objectives We previously showed that an angiotensin-converting enzyme inhibitor (captopril) or an angiotensin receptor blocker (losartan) reduced infarct size and improved endothelial function in a rat model of ischaemia-reperfusion. The present study was undertaken to see if aspirin (ASA) antagonised the beneficial effects of captopril or losartan. Methods One hundred and fourteen Sprague-Dawley rats were randomised into six groups; Control, ASA, captopril, losartan, ASA+captopril, and ASA+losartan. ASA, captopril or losartan were given at a concentration of 40 mg/kg/day in drinking water. After six weeks of pre-treatment, the rats were subjected to 17 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion, with haemodynamic and ECG monitoring. During the reperfusion period, the effective refractory period (ERP), ventricular fibrillation threshold (VFT) and bleeding time (BT) were measured. In fresh aortic rings precontracted with phenylephrine, endothelium-dependent and -independent relaxations were assessed using acetylcholine and nitroglycerin. Results Haemodynamic changes were not different between the groups. Serum ASA concentrations were 0.5, 1.1 and 0.6 mg/dl in the ASA, ASA+captopril and ASA+losartan groups, respectively, and BT was prolonged (p<0.01). ASA alone reduced endothelium-dependent relaxation (-29± 8 vs. -69±11%, p<0.01), but did not change endothelium-independent relaxation. ASA did not affect endothelial relaxation induced by acetylcholine in the presence of either captopril or losartan. Angiotensin I and ERP were elevated by captopril and losartan. Angiotensin II and VFT were elevated by losartan. ASA with captopril, captopril and losartan equally reduced infarct size, compared with control (39±3, 39±4 and 39±5 vs. 53±3%, all p<0.05). Conclusions Captopril and losartan had similar cardiovascular protective effects in a rat model of ischaemia-reperfusion. Aspirin did not attenuate the cardiovascular protective effects of captopril or losartan.
No involvement of the AT2-receptor in angiotensin II-enhanced sympathetic transmission in vitro
Authors: Nap Alexander , Balt Jippe C , Pfaffendorf Martin , van Zwieten Pieter A 
Published: May 2007

Angiotensin II (Ang II) enhances sympathetic neurotransmission via AT1-receptors located on sympathetic nerve terminals. We recently demonstrated that inhibition of Ang II-mediated facilitation in the pithed rat by irbesartan resulted in a U-shaped dose response curve, which was not observed when PD 123319, at a concentration that selectively blocks the AT2-receptor, was co-administered. Hence, the irbesartan-mediated `upstroke' might be explained by the involvement of the AT2-receptor after AT1blockade with high-dose irbesartan. In the present study, we further investigated the possible role of the AT2-receptor in Ang II-mediated facilitation in vitro.We studied the effect of the AT2-receptor antagonist PD 123319 (10 nM) on Ang II-enhanced sympathetic outflow evoked by electrical field stimulation (EFS) in the rat isolated inferior vena cava. Additionally, we investigated the effect of the AT1-receptor blocker irbesartan (0.1 nM—1 µM) on the sequelae of Ang II-enhanced, EFS-evoked sympathetic nerve traffic in the presence or absence of PD 123319 (10 nM).PD 123319 did not influence Ang II-enhanced sympathetic outflow. Irbesartan dose-dependently attenuate Ang II-augmented transmitter release (pIC507.99±0.03), whereas no U-shaped concentrationresponse relationship for irbesartan was observed. Co-administration of PD 123319 with irbesartan proved unable to influence Ang II-mediated facilitation differently compared with irbesartan alone. The experimental observations indicate that the AT2-receptor is not involved in Ang II-mediated enhancement of sympathetic nerve traffic in the present in vitro study.
Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance
Authors: Meune Christophe , Mourad Jean-Jacques , Bergmann Jean-François , Spaulding Christian 
Published: May 2007

Increased understanding of pathophysiological mechanisms of cardiovascular diseases has shown that the renin-angiotensin-aldosterone system (RAAS) is activated in this setting and suggests a central role for the angiotensin-converting enzyme (ACE). ACE transforms angiotensin I (Ang I) to angiotensin II (Ang II), and also promotes the degradation of bradykinin into inactive metabolites. These bradykinins stimulate nitric oxide synthesis and vasodilatator prostaglandin synthesis via a cyclooxygenase (COX) pathway. COX inhibitors may therefore be deleterious in cardiovascular disease and/or counteract part of ACE inhibitor (ACE-I) efficacy. This has been clearly demonstrated with non-steroidal anti-inflammatory drugs (NSAIDs), including high-dose aspirin, in avoiding their use in such patients. hypertension, coronary artery disease and chronic heart failure (CHF); most guidelines recommend avoiding their use in such patients. Theoretically, this effect is dose-mediated and the existence of an identical deleterious effect with low-dose aspirin has been an area of intense debate. In this article, we review studies, most of them conducted in CHF, that pointed out such a possible deleterious effect and a counteraction of ACE-Is with low-dose aspirin , using various criteria of assessment. However, there are no prospective long-term studies that have validated such an effect, and the role of other anti-aggregating agents has not been evaluated. Until such studies are published, the use of low-dose aspirin (100 mg/day) in such patients can be recommended.
Mineralocorticoid receptor blockade: new insights into the mechanism of action in patients with cardiovascular disease
Authors: Pitt Bertram , Stier Charles T , Rajagopalan Sanjay 
Published: May 2007

Mineralocorticoid receptor (MR) blockade is effective in reducing total mortality and the incidence of heart failure in patients with systolic left ventricular dysfunction (SLVD) associated with chronic heart failure or post myocardial infarction. Pre-clinical and clinical studies in SLVD have shown that MR blockade reduces sudden cardiac death, left ventricular remodelling, left ventricular hypertrophy, endothelial dysfunction, autonomic imbalance, renal dysfunction and improves fibrinolysis. While MR blockade promotes sodium excretion and the combination of an angiotensin-converting enzyme inhibitor and a MR blocker have been shown to be more effective than either alone in causing natriuresis, it is unlikely that their beneficial effects can be explained solely on this basis. Aldosterone has been shown to have a number of adverse effects, including activation of other neurohumeral mediators, stimulation of active reactive oxygen species (ROS), activation of the NF-κβ and AP-1 signalling pathways, vascular inflammation and fibrosis, myocardial hypertrophy, autonomic imbalance, and a decrease in fibrinolysis. MR blockade is, however, effective both in situations with and without an increase in serum aldosterone level, since the MR can be occupied and activated by cortisol as well as by aldosterone. In view of these mechanisms, MR blockade may play an important role not only on SLVD, but also in essential hypertension with normal systolic function, diastolic heart failure, valvular heart disease, vascular stiffening with ageing, progression of renal disease, and diabetes mellitus. This hypothesis will, however, require further prospective evaluation.
A rare combination consisting of aldosterone-producing adenoma and adrenal myelolipoma in a patient with heterozygosity for retinoblastoma (RB) gene
Authors: Caliumi Chiara , De Toma Giorgio , Bossini Alfredo , Cianci Rosario , Bosman Cesare , Genuardi Maurizio , Cerci Sabrina , Letizia Claudio 
Published: May 2007

Various pathological disorders have been associated with primary aldosteronism, including glucagonoma, phaeochromocytoma and primary hyperparathyroidism. In this report, a case of adrenal myelolipoma (a rare non-functioning tumour composed of mature adipose tissue and normal haematopoietic elements similar to bone marrow cells), aldosterone-producing adenoma and a pituitary microadenoma coexisting in a 62-year-old man with a 15-year history of arterial hypertension, previous ablation of an autonomously-functioning thyroid adenoma, multiple lipomas and an heterozygosity of the retinoblastoma (RB) susceptibility gene is reported. We believe that this case probably represents another variant of the multiple neoplasia syndrome and we speculate that structural alteration of the RB gene may play a role in the tumorogenesis.
Tonic levels of angiotensin II reduce tonic levels of vascular nitric oxide even in salt-replete man
Authors: Sim Justein SN , Farquharson Colin , Struthers Allan D 
Published: May 2007

Introduction Losartan improves stimulated endothelial function in patients with cardiovascular disease, but there are no data to establish whether losartan has this effect in normal man. Furthermore, whether losartan improves basal nitric oxide (NO) activity is controversial. We therefore examined whether treatment with losartan improved basal NO activity in normal, salt-replete man. If so, this would imply that tonic levels of angiotensin II (Ang II) reduce tonic basal levels of NO, even in salt-replete normal man. Methods We performed a randomised, placebo-controlled, double-blind crossover study in 24 healthy volunteers, comparing losartan 50 mg daily for one month versus placebo. Brachial artery endothelial function was assessed by bilateral venous occlusion plethysmography, measuring the response to intra-arterial infusions of the endothelial-dependent and endothelial-independent vasodilators, acetylcholine and sodium nitroprusside respectively and the endothelial-dependent vasoconstrictor NG-monomethyl-L-arginine. Results were analysed by multiple analysis of variance and statistical significance was taken as a p value of ≤ 0.05. Results Losartan significantly increased the vasoconstriction in response to N G-monomethyl-L-arginine (-37 2% vs. -32+2%, losartan vs. placebo; p=0.05). Losartan improved the vasodilatation response to acetylcholine; however, this result did not reach significance (214+2 0% vs. 174+20%, losartan vs. placebo; p=0.15). Losartan did not affect the response to nitroprusside (172+15% vs. 176+16%, losartan vs. placebo; p=0.84). There was no significant difference in blood pressure between the two study days. Conclusions Losartan improves basal NO bioactivity in healthy salt-replete volunteers. Even in salt-replete man, basal Ang II levels exert a tonic effect, which reduces basal NO.
Reassessing guidelines for heart failure
Authors: Drexler Helmut , Wollert Kai C 
Published: May 2007

Significant progress has been made in the last few years in the management of heart failure. In particular several trials have given significant results. It has become apparent that heart failure may be prevented in some patients by treatment of risk factors such as coronary artery disease. Experience with angiotensin-converting enzyme (ACE) inhibitors has shown that the survival and symptomatic benefits do last in the long term, and confirm that they are the first-line treatment in heart failure. The results of a number of trials using the angiotensin receptor blockers (ARBs) candesartan, valsartan and losartan are presented and discussed. There is also some experience now in the use of candesartan for patients with heart failure and preserved left ventricular systolic function. The COMET trial compared the β-blockers carvedilol and metoprolol tartrate, and suggests that there may be differences in clinical effect between β-blockers. The selective aldosterone receptor blocker eplerenone was evaluated in the EPHESUS trial in post-MI patients with signs of heart failure. Based on these clinical trials, heart failure guidelines are now being updated.
Statin therapy increases vascular sensitivity to angiotensin II in hypercholesterolaemic patients
Authors: Sim Justein SN , Dick John BC , Struthers Allan D 
Published: May 2007

Introduction Cross-talk between various cardiovascular risk factors has been suggested by a number of studies. This study examines the interaction between hypercholesterolaemia and the renin-angiotensin system in vivo in man. Methods We performed a randomised, placebo-controlled, double-blind crossover study on 40 hypercholesterolaemic patients, comparing cholesterol-lowering therapy with a statin for six months versus placebo. Brachial artery function was assessed by bilateral venous occlusion plethysmography using intra-arterial infusions of the endothelial-dependent vasoconstrictors, angiotensin I (Ang I) and angiotensin II (Ang II), to measure vascular angiotensin-converting enzyme (ACE) and Ang II receptor response respectively. The endothelial-independent vasoconstrictor, noradrenaline, was used as a control vasoconstrictor. Results were analysed by multiple analysis of variance and statistical significance Cholesterol-lowering treatment with a statin was taken as a p value <0.05. Results Cholesterol-lowering treatment with alstatin significantly reduced the mean total cholesterol level to 5.71 mmol/L vs. 7.57 mmol/L on placebo (p<0.0001). Hypercholesterolaemia significantly increased the vasoconstriction response to noradrenaline (placebo versus statin treatment; p=0.046). In hypercholesterolaemia, there was a strong trend towards a reduction in the vasoconstriction response to Ang I (placebo versus statin treatment; p=0.089). In hypercholesterolaemia, the vasoconstriction response to Ang II was significantly reduced (placebo versus statin treatment; p=0.01). Conclusions Our in vivo results show that, unlike some other previous work, hypercholesterolaemia is associated with down-regulation of the vasoconstrictor response to Ang II and that statin therapy up-regulates the local vasoconstrictor response to Ang II. The possibility now arises that, in man, statins alter the balance between AT1-receptors and AT2-receptors.
Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers
Authors: Madrid Antonio H , Marín Irene Marín , Escobar Cervantes Carlos , Bernal Morell Enrique , Escudero Estévez Jaime , Moreno Gerardo , Rondón Parajón Jorge , Jian Peng  , Limón Lilianna , Nannini Sebastian , Moro Concepción 
Published: May 2007

Background Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. Methods and results Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (`lone AF'), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard 0.27—0.82; p=0.001). ratio for a recurrence in group III: 0.47 (95% CI Conclusions The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.
Angiotensin II may mediate apoptosis via AT1-receptors in the rat cardiac conduction system
Authors: Vongvatcharanon Uraporn , Vongvatcharanon Surapong , Radenahmad Nisaudah , Kirirat Pornpimol , Intasaro Pranom , Sobhon Prasert , Parker Terry 
Published: May 2007

Introduction Apoptosis and angiotensin II (Ang II) have been suggested as possible causes of arrhythmias. In addition, Ang II via Ang II type I (AT1-) receptors, has been demonstrated to induce cardiomyocyte apoptosis. The transgenic m(Ren-2)27 (TG) rat carries the additional Ren-2 gene, the expression of which results in an increase in cardiac Ang II, thus potentially affecting the cell growth/death equilibrium. In this study we have investigated the effect of Ang II, via AT1-receptors, on mediating apoptosis in a cardiac conduction system (SA node and AV nodes). Materials and methods Heart sections from male two-day, one-week and two-week TG and Sprague-Dawley (SD) rats were stained with Masson Trichrome to localise the SA and AV nodes. The sections containing SA or AV nodes were processed for quantitation of apoptotic nuclei and AT1-receptors. Results The number of apoptotic nuclei/mm2 in the SA and AV nodes were found to decrease from two days to two weeks in both the TG and the SD rats, and the number of apoptotic nuclei/mm2 in the TG groups was significantly higher than that of the SD groups for all ages (p<0.05). The number of AT1-receptors/mm2 in the SA node were found to decrease with increasing age, whereas the number of AT1-receptors/mm 2 in the AV node was increased in both TG and SD rats and the number of AT1-receptors/mm2 in the three TG groups was significantly more than that of the three SD groups (p<0.05). Discussion and conclusion As a consequence of the additional renin gene in the TG rats, which results in the alteration of the local renin-angiotensin system, the numbers of AT1-receptors/mm 2 and apoptotic nuclei/mm2 are increased. The number of apoptotic nuclei/mm2 and AT1-receptors/mm2 in the SA node decrease with maturation, whereas, the number of AT1-receptors in the AV node increase. Thus, there may be a correlation between Ang II and apoptosis in the SA node, which does not appear to be present in the AV node.