Role of urotensin II in patients on dialysis

Totsune, Kazuhito; Takahashi, Kazuhiro; Arihara, Zenei; Sone, Masahiko; Satoh, Fumitoshi; Ito, Sadayoshi; Kimura, Yuichiro; Sasano, Hironobu; Murakami, Osamu

doi:10.1016/s0140-6736(01)06002-0

Cited by 199 publications

(165 citation statements)

References 4 publications

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“…14 Our measurements of plasma UTN in control subjects contrast with other published work with smaller numbers of subjects. [15][16][17] Matsushita et al 15 reported undetectable levels, but the lower limit of the UTN assay was insensitive at Ϸ36 fmol/mL. Our values are in between those reported by Totsune et al 16 (4.4 fmol/mL) and Wilkinson et al 17 (12 fmol/mL).…”

Section: Discussionsupporting

confidence: 64%

Plasma Urotensin in Human Systolic Heart Failure

et al. 2002

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Background-Human urotensin II (UTN) has potent vasoactive and cardiostimulatory effects, acting on the G protein-linked receptor GPR14. Myocardial UTN expression is upregulated in heart failure, and UTN stimulates myocardial expression of the natriuretic peptides. We investigated plasma UTN levels in heart failure (HF; left ventricular systolic dysfunction) in comparison with plasma N-terminal pro-brain natriuretic peptide (N-BNP) levels. Methods and Results-N-BNP and UTN were measured in plasma from 126 patients with HF and 220 age-and sex-matched controls. Both peptides were elevated in plasma of HF patients and were correlated (r s ϭ0.35, PϽ0.001).In contrast to N-BNP, there was no relationship of plasma UTN with New York Heart Association (NYHA) class. Although plasma N-BNP showed a positive relationship with age and female sex, there was no such age-dependent change in plasma UTN, and control women had lower levels compared with control men. Receiver operating characteristic curves for the diagnosis of HF had areas of 0.90 and 0.86 for N-BNP and UTN, respectively (PϽ0.001 for both). Receiver operating characteristic curve area for diagnosis of NYHA class I HF with UTN was better than that with N-BNP. Conclusions-Plasma UTN is elevated in HF, which suggests a pathophysiological role for this peptide. Plasma UTN may be a useful alternative to N-BNP in the diagnosis of HF, inasmuch as its levels are elevated irrespective of age, sex, or NYHA class.

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Section: Discussionsupporting

confidence: 64%

Plasma Urotensin in Human Systolic Heart Failure

et al. 2002

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“…Alternatively, in certain pathological conditions including diabetes (24)(25)(26)(27)50), the plasma concentrations of UII may attain much higher levels (140-420 pg/ml) that are in the same range as the IC 50 value (120 pmol/l i.e. 167 pg/ml) calculated for the insulinostatic activity of UII, suggesting that UII might constitute a diabetogenic factor.…”

Section: Discussionmentioning

confidence: 86%

“…Immunoreactive UII is readily measurable in human plasma, and the circulating levels of UII are elevated in patients with chronic renal failure (24) and heart failure (25,26). Plasma UII levels are also increased in diabetic patients with or without proteinuria, but are not correlated with fasting blood glucose or HbA1c levels (27).…”

Section: Introductionmentioning

confidence: 99%

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

Silvestre

Egido

Hernández

et al. 2004

European Journal of Endocrinology

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Objective: Previous work from our laboratory has demonstrated that frog urotensin-II (UII), at a high concentration, inhibits glucose-induced insulin release in the rat pancreas. We have investigated the effect of rat UII and two structural analogs on insulin secretion and searched for the presence of UII-immunoreactivity in rat pancreatic extracts. Methods: The study was performed in the perfused rat pancreas. UII as well as its analogs were synthesized by solid phase methodology. Pancreatic extracts were analyzed for UII by reversed-phase HPLC combined with a sensitive UII RIA. Results: Infusion of synthetic rat UII inhibited glucose-induced insulin release in a dose-dependent manner (IC 50 : 0.12 nmol/l). UII (1 nmol/l) also inhibited the insulin responses induced by carbachol, glucagon-like peptide-1, and a calcium channel agonist (BAY K 8644). The inhibitory effect of UII was mimicked by the potent G protein-coupled receptor (GPR14) agonist [3-iodo-Tyr 6 ]UII(4 -11). In contrast, [Ala 8 ]UII(4 -11), a UII analog devoid of contractile activity on rat aortic rings, did not affect glucose-induced insulin secretion. Analysis of rat pancreatic extracts revealed the presence of an immunoreactive peptide exhibiting the same retention time as synthetic rat UII.Conclusions: Our results demonstrate that UII is a potent insulinostatic peptide. The observation that UII is actually present in the pancreas suggests that this peptide may play a physiological role in the control of insulin secretion. Concerning the two UII analogs tested, only ]UII(4 -11), reportedly possessing GPR14-mediated contractile activity, mimics the insulinostatic effect of UII. This finding would support the view that UII acts on the pancreatic beta cell through the GPR14 receptor.European Journal of Endocrinology 151 803-809

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“…Plasma UTN is much increased in patients with renal diseases, including minimal change glomerulopathy, 41 diabetic nephropathy, 42 chronic kidney disease in general, 24 and ESRD in particular. 19,20 …”

Section: Urotensin In Renal Diseases and In Esrdmentioning

confidence: 99%

“…19,20 In previous studies in this population we found that UTN is inversely, rather than directly, related to CV stress hormones like norepinephrine and neuropeptide Y 20 and to the endogenous inhibitor of NO synthesis, asymmetrical dimethylarginine (ADMA). 21 UTN is a potent NOdependent vasodilator in pulmonary and mesenteric circulation in humans, 22 and we hypothesized that these links may serve to mitigate the high risk associated with sympathetic overactivity and NO inhibition in ESRD.…”

mentioning

confidence: 95%

Urotensin II and Cardiomyopathy in End-Stage Renal Disease

et al. 2008

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Abstract-Circulating urotensin (UTN) is increased in patients with heart failure and in patients with renal diseases, and UTN antagonism is currently considered as a potential treatment for these conditions. Contrary to this contention, studies in end-stage renal disease suggest that, perhaps because of interference with sympathetic and NO systems, UTN may be cardioprotective. (UTN) is a cyclic undecapeptide that is widely distributed in several organ systems, including the vascular system and the heart. 1 UTN is a quite strong inotrope in isolated myocardial tissues like human right atrial trabeculae 2 and rat left ventricular (LV) papillary muscles, 3 but in vivo it reduces cardiac performance when administered on a chronic basis in the rat 4 and causes a marked cardiodepressant effect in acute experiments in primates 5,6 concomitant with a decrease in blood pressure. Because UTN promotes myocardial cell hypertrophy in vitro and activates fibrogenesis, 7,8 high gene expression of this peptide at myocardial level 9 and high circulating UTN in patients with heart failure 10 -13 have initially been considered as potentially noxious in these patients. However, recent observations in a chronic volume overload model in the rat 14 indicate that subcutaneous administration of UTN on a chronic basis may help to preserve myocardial contractility in this model. These observations go along with findings in the same model showing that bolus UTN injections exert favorable, NOdependent, renal hemodynamic effects. 15 On the other hand, UTN is reduced in patients with acute coronary syndromes, 16 and low UTN predicts adverse clinical outcomes and death in patients after myocardial infarction. 17 Overall it remains largely undefined whether UTN has a role in LV disorders in humans.End-stage renal disease (ESRD) represents an intriguing model to explore the role of UTN in cardiovascular (CV) diseases in humans because cardiomyopathy is pervasive in this condition 18 and because UTN attains high plasma levels in ESRD. 19,20 In previous studies in this population we found that UTN is inversely, rather than directly, related to CV stress hormones like norepinephrine and neuropeptide Y 20 and to the endogenous inhibitor of NO synthesis, asymmetrical dimethylarginine (ADMA). 21 UTN is a potent NOdependent vasodilator in pulmonary and mesenteric circulation in humans, 22 and we hypothesized that these links may

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Role of urotensin II in patients on dialysis

Cited by 199 publications

References 4 publications

Plasma Urotensin in Human Systolic Heart Failure

Plasma Urotensin in Human Systolic Heart Failure

Urotensin-II is present in pancreatic extracts and inhibits insulin release in the perfused rat pancreas

Urotensin II and Cardiomyopathy in End-Stage Renal Disease

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