Expressions of irisin and urotensin II and their relationships with blood pressure in patients with preeclampsia.

The aims of this study are to observe irisin and urotensin II (UII) levels in serum and placenta in normal pregnant and preeclamptic women and investigate the relationship between expressions irisin and UII, and their association with blood pressure. A total of 67 pregnant subjects were recruited, including 31 healthy and 36 preeclamptic pregnant women. Serum irisin and UII concentrations were measured. Expressions of fibronectin type III domain-containing protein 5 (FNDC5) (irisin precursor) and UII in placenta specimens were performed. There was no significant difference of serum irisin levels between severe preeclamptic (SPE)) patients, mild preeclamptic (MPE) patients and normal controls, while serum UII was significantly higher in preeclamptic women than normal pregnancy. There was no relationship between serum UII and irisin levels. In patients with preeclampsia, serum irisin was negatively associated with systolic and diastolic blood pressure(r = -0.350, P = 0.004, r = -0.307, P = 0.011), while serum UII was positively associated with systolic blood pressure (r = 0.291, P = 0.031). Serum irisin, UII, urinary protein level, BMI and serum creatinine were the independent determinants of blood pressure in preeclampsia by multiple regression analysis. Protein expression of FNDC5 and UII was upregulated in placenta of patients with SPE and positively correlated with systolic blood pressure and urinary protein level. We firstly verify that serum irisin and placental irisin precursor expressions have differently correlated with blood pressure. Expressions of irisin and urotensin II have relationships with blood pressure in patients with preeclampsia.

Urotensin II and renal function in the rat.

Urotensin II (UII) is a potent vasoactive hormone in mammals. However, despite its well-known effects on epithelial sodium transport in fish, little is known about its actions on the mammalian kidney. The aim of this study was to determine the effects of UII on renal function in the rat. Using standard clearance methods, the effects of rUII and the rat UII receptor (UT) antagonist, urantide, were studied. UII was measured in plasma and urine by radioimmunoassay. UII and UT were localized in the kidney by immunohistochemistry and mRNA expression quantified. Rat urinary [UII] was 1,650-fold higher than that in plasma. Immunoreactive-UII was localized to the proximal tubules, outer and inner medullary collecting ducts (IMCD); UT receptor was identified in glomerular arterioles, thin ascending limbs, and IMCD. UII and UT mRNA expression was greater in the medulla; expression was higher still in spontaneously hypertensive rats (SHRs) associated with raised plasma (UII). Injection of rUII induced reductions in glomerular filtration rate (GFR), urine flow, and sodium excretion. Urantide infusion resulted in increases in these variables. Endogenous UII appears to contribute to the regulation of GFR and renal sodium and water handling in the rat. While hemodynamic changes predominate, we cannot rule out the possibility of a direct tubular action of UII. Increased expression of UII and UT in the SHR suggests that UII plays a role in the pathophysiology of cardiovascular disease.

Urotensin-II levels in children with minimal change nephrotic syndrome.

Human urotensin-II (hU-II) is the most potent mammalian vasoconstrictor identified to date. Although it is expressed mainly in the brain and spinal cord, it is also detected in other tissues, such as the kidney. It has been speculated that U-II might be an important physiological mediator of vascular tone and blood pressure in humans. To our knowledge, no studies have investigated the level of U-II in children with minimal change nephrotic syndrome (MCNS). Considering the renal synthesis and vasoactive role of U-II, we aimed to measure the plasma and urinary levels of U-II in children with MCNS, and investigate the correlation with other clinical and laboratory findings. Twenty-six children with clinical MCNS, ranging in age from 2 to 7 years, were compared with 16 healthy age- and sex-matched controls. The median age of the children was 4.73+/-2.36 years. U-II level was measured by RIA. Plasma U-II concentrations (pg/ml) were decreased during relapse (20.11+/-14.43 in relapse, 38.94+/-23.86 in remission, P<0.05), whereas urinary U-II levels (pg/mg urinary creatinine) were significantly higher in relapse than in remission (37.31+/-28.43 in relapse, 31.09+/-21.10 in remission, P<0.05). We could not detect any relationship between U-II levels and other clinical and laboratory parameters. Our data indicate that the important changes in plasma and urinary U-II levels during relapse may be the result of heavy proteinuria rather than playing a role in mediating the clinical and laboratory manifestations of MCNS in children.

Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with Type 2 diabetes mellitus: association with progress of diabetic nephropathy.

Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. In order to clarify the pathophysiological role of UII in diabetes mellitus, we examined plasma immunoreactive UII levels and urinary excretion of immunoreactive UII in 10 control subjects and 48 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to the renal function: Group I with Ccr > or = 70 ml/min, group II with 30 < or = Ccr <70 ml/min and group III with Ccr <30 ml/min. Plasma immunoreactive UII levels were elevated in the three diabetic groups compared with normal controls (P <0.05). Group III patients had significantly higher plasma immunoreactive UII levels (15.9 +/- 2.2 fmol/ml, mean +/- S.E.M., n=6) by approximately 1.6-fold than did group I (10.9 +/- 0.9 fmol/ml, n=17) and group II (10.8 +/- 0.8 fmol/ml, n=25) (P <0.05). Urinary excretion of immunoreactive UII was significantly increased in group III patients (52.4 +/- 14.8 pmol/day) by more than 1.8-fold compared with control subjects, groups I and II (P <0.005). Fractional excretion of immunoreactive UII significantly increased as renal function decreased. Presence of diabetic retinopathy or neuropathy had negligible effects on plasma immunoreactive UII levels and urinary immunoreactive UII excretion. Reverse phase HPLC analyses showed three immunoreactive peaks in normal plasma extracts and multiple immunoreactive peaks in normal urine extracts. Thus, Type 2 diabetes mellitus itself is a factor to elevate plasma immunoreactive UII levels, and accompanying renal failure is another independent factor for the increased plasma immunoreactive UII levels in Type 2 diabetic patients. Increased urinary immunoreactive UII excretion in Type 2 diabetic patients with advanced diabetic nephropathy may be due not only to the elevated plasma immunoreactive UII levels but also to increased UII production and/or decreased UII degradation in the diseased kidney.

Differential levels of "urotensin-II-like" activity determined by radio-receptor and radioimmuno-assays.

Plasma and urinary levels of "urotensin(U)-II-like" substances determined in healthy human volunteers were 12.4 +/- 0.6 ng/ml and 2.2 +/- 0.3 ng/ml by RIA, an order of magnitude lower than that seen by RRA, 167.5 +/- 9.5 ng/ml and 65.2 +/- 4.3 ng/ml. HPLC demonstrated the existence of at least three prominent activity peaks in plasma and urine, the more hydrophobic of which did not co-elute with U-II, degradation products or URP. RRA and RIA recognized these peaks with contrasting efficacy. As such, published levels of "U-II-like" activity should be interpreted with caution until a better understanding is obtained regarding what species specific RIA and RRA assay reagents interact with.

Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues.

BACKGROUND: Urotensin-II (UII), a cyclic dodecapeptide originally isolated from fish urophysis that has potent cardiovascular effects, has recently been identified as an endogenous ligand for the orphan G protein-coupled receptor, GPR14. The physiological roles of endogenous UII and its receptor in humans remain unknown. OBJECTIVE: To investigate the presence of human (h) UII-like immunoreactivity (hUII-LI) in human biological fluids, and the expression of hUII and GPR14 genes in human tissues. METHODS: We have established a specific radioimmunoassay for hUII and the real-time quantitative reverse transcriptase polymerase chain reaction method using LightCycler for the quantification of hUII and GPR14 mRNAs. RESULTS: Gel filtration and reverse-phase high performance liquid chromatography of human urine extracts revealed a single major peak of hUII-LI co-eluting with known hUII. The concentrations of hUII-LI in urine from normal individuals were 7.4 +/- 0.9 microg/g creatinine, whereas its plasma concentration was undetectable (< 50 pg/ml). Urinary hUII concentrations from patients with essential hypertension and those with renal tubular abnormality, but not with glomerular diseases, were significantly greater than those from normal individuals. The resulting fractional excretion of hUII, exceeding the glomerular filtration rate, suggests a renal origin of urinary UII-LI. hUII mRNAs were abundantly expressed in the kidney and the right atrium, but far less so in the vasculature, whereas GPR14 mRNAs were equally and abundantly expressed in both cardiovascular and renal tissues. CONCLUSIONS: These data suggest that urinary hUII is derived mainly from a renal source, and that hUII functions as an autocrine/paracrine vasoactive factor not only in the cardiovascular system, but also in the kidney, with an as yet unspecified function.