Elevated plasma endothelin concentrations in heart failure; an effect of angiotensin II?

Good, J. M.; Nithoyannopoulos, P.; Ghatei, Mohammad A.; Crossman, David C.; Bloom, Stephen R.; Clark, P.; Oakley, Celia M.; Cleland, JG

doi:10.1093/oxfordjournals.eurheartj.a060446

Cited by 39 publications

(13 citation statements)

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“…Evidence shows that the RAS is activated during ischemia and reperfusion, with the Ang II peptide being one of the main causes of the cardiac damage. [21][22][23] Reperfusion arrhythmias are associated with changes in Ca +2 levels and it is well established that Ang II not only stimulates Ca +2 influx through Ca +2 channels but also induces release of intracellular Ca +2 , resulting in excess of Ca +2 inside the cells during ischemia/ reperfusion injury. 8 …”

Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of angiotensin A: A novel peptide of the renin–angiotensin system

Coutinho

Foureaux

Rodrigues

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction: Angiotensin (Ang) A was first identified in human plasma and it differs from Ang II in Ala 1 instead of Asp 1 . Here, we hypothesized that the actions of this peptide might explain, at least partially, the limited effects of AT 1 R antagonists in certain cardiovascular diseases. Materials and methods:The effects of Ang A and Ang II on blood pressure (BP) and heart function were compared. Importantly, participation of AT 1 R in these effects was evaluated. Furthermore, the effects of these two peptides on ischemia/reperfusion arrhythmias and involvement of calcium in these effects were investigated. Results: Administration of increasing doses of these peptides caused elevations in BP at comparable magnitude. AT 1 R blockade completely abolished these effects. The actions of these peptides in cardiac function were quite similar although the effects of Ang A were only partially blocked by losartan. Interestingly, Ang II elicited an increase in the duration of ischemia/reperfusion arrhythmias while Ang A had no effect on cardiac rhythm during reperfusion. In accordance, differently to Ang II, Ang A did not induce any significant effect on calcium transient during baseline and ischemic stress conditions. Conclusions: These data suggest that the existence of alternative peptides of the renin-angiotensin system (RAS) might contribute to the limited effects of angiotensin receptor blockers (ARBs) in certain pathophysiological circumstances.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of angiotensin A: A novel peptide of the renin–angiotensin system

Coutinho

Foureaux

Rodrigues

et al. 2013

J Renin Angiotensin Aldosterone Syst

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“…There is increasing interest in the role of pulmonary hypertension and right heart dysfunction in patients with heart failure, which seem to be better guides to prognosis than left ventricular dysfunction (Damy et al, 2010). Plasma ET is more closely related to pulmonary vascular resistance than other hemodynamic features of heart failure and this relationship may be causal (Cody et al, 1992;Givertz et al, 2000;Good et al, 1994;Ooi et al, 2002). Thus, ET could be an important driver of this pathway of progression of heart failure.…”

Section: Endothelin In Heart Failurementioning

confidence: 99%

Clinical trials with endothelin receptor antagonists: What went wrong and where can we improve?

et al. 2012

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In the early 1990s, within three years of cloning of endothelin receptors, orally active endothelin receptor antagonists (ERAs) were tested in humans and the first clinical trial of ERA therapy in humans was published in 1995. ERAs were subsequently tested in clinical trials involving heart failure, pulmonary arterial hypertension, resistant arterial hypertension, stroke/subarachnoid hemorrhage and various forms of cancer. The results of most of these trials - except those for pulmonary arterial hypertension and scleroderma-related digital ulcers - were either negative or neutral. Problems with study design, patient selection, drug toxicity, and drug dosing have been used to explain or excuse failures. Currently, a number of pharmaceutical companies who had developed ERAs as drug candidates have discontinued clinical trials or further drug development. Given the problems with using ERAs in clinical medicine, at the Twelfth International Conference on Endothelin in Cambridge, UK, a panel discussion was held by clinicians actively involved in clinical development of ERA therapy in renal disease, systemic and pulmonary arterial hypertension, heart failure, and cancer. This article provides summaries from the panel discussion as well as personal perspectives of the panelists on how to proceed with further clinical testing of ERAs and guidance for researchers and decision makers in clinical drug development on where future research efforts might best be focused.

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“…In addition, several studies have reported that angiotensin II stimulates production of reactive oxygen species (ROS)in vascular smooth muscle cells via NADH/NADPH oxidase activation [13,14]. It has been proposed that angiotensin II levels are elevated in ischemic heart disease [15,16], liver injury [17], cerebral ischemia [18] and renal injury [19]. Furthermore, angiotensin I-converting enzyme inhibition, which decreases the production of angiotensin II, has been shown to improve postischemic injury in both animal and human studies [20,21].…”

Section: Introductionmentioning

confidence: 99%

CV-11974, angiotensin II type I receptor antagonist, reduces the severity of indomethacin-induced rat enteritis

et al. 2007

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The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on indomethacin-induced small intestinal injury in rats. Single administration of indomethacin provoked severe inflammatory lesions in the small intestine. The levels of thiobarbituric acid-reactive substances (TBARS), myeloperoxidase (MPO) activities and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in the indomethacin-treated group compared with the sham group. In addition, the angiotensin II type I receptor was increased in the small intestine after the administration of indomethacin. The development of intestinal lesions in response to indomethacin was prevented by pretreatment with CV-11974 together with significant suppression of the increased level of TBARS, MPO activities and CINC-1. These results indicate that CV-11974 protected against the small intestinal damage elicited by indomethacin, which suggests that angiotensin II/AT1 receptor interaction is involved in the pathogenesis of the intestinal inflammation associated with oxidative stress.

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Elevated plasma endothelin concentrations in heart failure; an effect of angiotensin II?

Cited by 39 publications

References 0 publications

Cardiovascular effects of angiotensin A: A novel peptide of the renin–angiotensin system

Cardiovascular effects of angiotensin A: A novel peptide of the renin–angiotensin system

Clinical trials with endothelin receptor antagonists: What went wrong and where can we improve?

CV-11974, angiotensin II type I receptor antagonist, reduces the severity of indomethacin-induced rat enteritis

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