Der Urotensin II Rezeptorantagonist Palosuran senkt den Pfortaderdruck und verbessert die renale Funktion in zirrhotischen Ratten mit Aszites

Urotensin II (UTS) is a potent vasoactive peptide that was originally identified in teleost fish. Mammalian orthologues of UTS and its receptor (UTSR) have been described in several species, including humans and rats. We have shown previously that bolus injections of UTS caused a decrease in urine flow and sodium excretion rates in parallel with marked reductions in renal blood flow (RBF) and glomerular filtration rate (GFR). The aim of this study was to determine the effect of UTS infusion at a dose that has minimal impact upon renal haemodynamics in order to identify a potential direct tubular action of UTS. Infusion of rat UTS (rUTS) at 0.6 pmol/min per 100 g body weight in male Sprague–Dawley rats, which had no effect on RBF and caused a 30% reduction in GFR, resulted in a significant increase in the fractional excretion of sodium (vehicle 2.3±0.6 versus rUTS 0.6 pmol 4.5±0.6%, P<0.05) and potassium. At the higher dose of 6 pmol/min per 100 g body weight, haemodynamic effects dominated the response. rUTS induced a marked reduction in RBF and GFR (vehicle 1.03±0.06 versus rUTS 6 pmol 0.31±0.05 ml/min per 100 g body weight, P<0.05) resulting in an anti-diuresis and anti-natriuresis, but no change in fractional excretion of sodium or potassium. Uts2d and Uts2r mRNA expression were greater in the renal medulla compared with the cortex. Together, these data support an inhibitory action of Uts2d on renal tubule sodium and potassium reabsorption in the rat, in addition to its previously described renal haemodynamic effects.

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Urotensin II is an Autocrine/Paracrine Growth Factor for the Porcine Renal Epithelial Cell Line, LLCPK1

Endocrinology ◽

10.1210/en.2003-0029 ◽

2003 ◽

Vol 144 (5) ◽

pp. 1825-1831 ◽

Cited By ~ 49

Author(s):

Mika Matsushita ◽

Masayoshi Shichiri ◽

Nozomi Fukai ◽

Naoko Ozawa ◽

Takanobu Yoshimoto ◽

...

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Kinase Inhibitor ◽

Epithelial Cell Line ◽

Urotensin Ii ◽

Renal Epithelial Cell ◽

Renal Epithelial Cells ◽

Kinase C ◽

Renal Epithelial Cell Line ◽

Paracrine Growth Factor

Urotensin-II (UII), a cyclic dodecapeptide with potent cardiovascular effects, has recently been shown to be abundantly expressed in the human kidney and excreted in human urine. To investigate whether UII acts as an autocrine/paracrine growth factor for renal epithelial cells, we have studied the effects of human UII (hUII) on DNA synthesis, cytosolic free Ca2+ concentration ([Ca2+]i), ERK activation, and protooncogene (c-myc) expression in a porcine renal epithelial cell line (LLCPK1). hUII stimulated [3H]thymidine uptake into quiescent cells in a dose-dependent manner (10−9 to 10−7m); this effect was inhibited by a protein kinase C inhibitor (GF109203X), a MAPK kinase inhibitor (PD98059), and a calcium channel blocker (nicardipine). Neither phosphatidyl inositol-3 kinase inhibitors (LY294002, wortmannin) nor p38 kinase inhibitor (SB203580) affected the hUII-induced DNA syntheses. hUII rapidly (within 5 min) and dose-dependently (10−9 to 10−7m) increased [Ca2+]i in fura-2-loaded cells. hUII also caused a rapid and transient activation of ERK1/2 and induction of c-myc. LLCPK1 cells expressed UII mRNA and its receptor GPR14 mRNA, as determined by RT-PCR, and released UII-like immunoreactivity into media. Neutralization of endogenous UII by anti-hUII antibody, but not nonimmune serum, significantly suppressed DNA synthesis. These data suggest that hUII is an autocrine/paracrine growth factor for renal epithelial cells via activation of both protein kinase C and ERK1/2 pathways as well as Ca2+ influx via voltage-dependent Ca2+ channels.

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Urotensin II inhibits arginine vasotocin and stimulates isotocin release from nerve endings in the pituitary of gilthead sea bream (Sparus aurata)

Journal of Experimental Zoology Part A Ecological Genetics and Physiology ◽

10.1002/jez.1875 ◽

2014 ◽

Vol 321 (8) ◽

pp. 467-471 ◽

Cited By ~ 1

Author(s):

Hanna Kalamarz-Kubiak ◽

Iris Meiri Ashkenazi ◽

Agnieszka Kleszczyńska ◽

Hanna Rosenfeld

Keyword(s):

Sparus Aurata ◽

Arginine Vasotocin ◽

Nerve Endings ◽

Gilthead Sea Bream ◽

Sea Bream ◽

Urotensin Ii

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Enhanced renal sensitivity of the spontaneously hypertensive rat to urotensin II

AJP Renal Physiology ◽

10.1152/ajprenal.90374.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. F1239-F1247 ◽

Cited By ~ 10

Author(s):

Alaa E. S. Abdel-Razik ◽

Richard J. Balment ◽

Nick Ashton

Keyword(s):

Renal Function ◽

Spontaneously Hypertensive Rat ◽

Renal Medulla ◽

Fractional Excretion ◽

Urotensin Ii ◽

Spontaneously Hypertensive ◽

Wky Rats ◽

Hypertensive Rat ◽

Fractional Excretion Of Sodium ◽

Wistar Kyoto

Urotensin II (UII) has been implicated widely in cardiovascular disease. The mechanism(s) through which it contributes to elevated blood pressure is unknown, but its emerging role as a regulator of mammalian renal function suggests that the kidney might be involved. The aim of this study was to determine the effect of UII on renal function in the spontaneously hypertensive rat (SHR). UII infusion (6 pmol·min−1·100 g body wt−1) in anesthetized SHR and control Wistar-Kyoto (WKY) rats produced marked reductions in glomerular filtration rate (ΔGFR WKY, n = 7, −0.3 ± 0.1 vs. SHR, n = 7, −0.6 ± 0.1 ml·min−1·100 g body wt−1, P = 0.03), urine flow, and sodium excretion rates, which were greater in SHR by comparison with WKY rats. WKY rats also showed an increase in fractional excretion of sodium (ΔFENa; +0.6 ± 0.1%, P = 0.02) in contrast to SHR in which no such change was observed (ΔFENa −0.6 ± 0.2%). Blockade of the UII receptor (UT), and thus endogenous UII activity, with urantide evoked an increase in GFR which was greater in SHR (+0.3 ± 0.1) compared with WKY rats (+0.1 ± 0.1 ml·min−1·100 g body wt−1, P = 0.04) and was accompanied by a diuresis and natriuresis. UII and UT mRNA expression were greater in the renal medulla than the cortex of both strains; however, expression levels were up to threefold higher in SHR tissue. SHR are more sensitive than WKY to UII, which acts primarily to lower GFR thus favoring salt retention in this model of hypertension.

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