Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries

Stirrat, Alison; Gallagher, Marie; Douglas, Stephen A.; Ohlstein, Eliot H.; Berry, C. L.; Kirk, Alan; Richardson, Michael R.; MacLean, Margaret R.

doi:10.1152/ajpheart.2001.280.2.h925

Cited by 143 publications

(116 citation statements)

References 12 publications

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“…The response is limited to large elastic vessels and does not include small resistance vessels. On the other side, UII can also promote vasodilation via an endothelium-dependent nitric oxide (NO)-mediated response (Bottrill et al 2000, Stirrat et al 2001. It is difficult to describe the effects of UII in vivo as they have not been conserved during evolution.…”

Section: Uts2r5mentioning

confidence: 99%

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Tostivint¹,

Daza²,

Bergqvist³

et al. 2014

Journal of Molecular Endocrinology

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Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand-receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1-6) genes, on the one hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1-5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception of SSTR4. Moreover, several additional genes have been gained through the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5 genes, and through local duplications, such as SS3. In mammals, all the genes of the SSTR family have been preserved, with the exception of SSTR6. In contrast, for the other families, extensive gene losses occurred, as only the SS1, SS2, UII, and URP genes and one UTS2R gene are still present.

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Section: Uts2r5mentioning

confidence: 99%

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Tostivint¹,

Daza²,

Bergqvist³

et al. 2014

Journal of Molecular Endocrinology

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mentioning

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. 23 This hypothesis was corroborated by cognate observations showing that high plasma UTN predicts better clinical outcomes, ie, reduced CV complications in ESRD 23 and longer survival in patients with stage 3 to 4 chronic kidney disease.…”

mentioning

confidence: 99%

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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“…3 There are important species differences in the reactivity of different vessels to UTN. For example, UTN vasoconstricts monkey vessels, vasodilates human pulmonary vasculature and mesenteric resistance vessels, 4 and has no effect on human subcutaneous resistance vessels. 5 UTN also causes vascular smooth muscle hypertrophy.…”

mentioning

confidence: 99%

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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Potent vasodilator responses to human urotensin-II in human pulmonary and abdominal resistance arteries

Cited by 143 publications

References 12 publications

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Urotensin II and Cardiomyopathy in End-Stage Renal Disease

Plasma Urotensin in Human Systolic Heart Failure

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