Up-regulation of the endothelin receptor A in placental tissue from first trimester delayed miscarriages.

OBJECTIVE: This study tested the hypothesis that the endothelin (ET)/ET receptor (ETR) system in biologic fluids and in the human placenta is altered in delayed miscarriages as compared to apparently normal early pregnancies (reference group). METHODS: Immunoreactive ET (irET) concentrations were measured in plasma, urine, and cervical smears from 57 pregnant women in the weeks 6 to 14 of gestation (46 delayed miscarriages, 11 references) with radioimmunoassay (RIA). ET-1, ETR-A, and ETR-B mRNA, and ETR protein expression were measured in placental tissue of 45 early pregnancies (31 delayed miscarriages, 14 references) using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting, respectively. RESULTS: irET levels in plasma, urine, and cervical smears did not differ between groups. Two prevailing ETR-A and ETR-B proteins were found at 45 and 55 kd, and were distributed similarly in delayed miscarriages and references. ETR-A protein and mRNA levels were 54% (P = .009) and threefold (P = .021) higher, respectively, in delayed miscarriages versus references. There was no difference in placental ETR-B and ET-1 mRNA levels between groups. CONCLUSION: Neither irET nor ET-1 mRNA levels differ between delayed miscarriages and normal early pregnancies. Pregnancies at risk for miscarriage cannot be identified by measurement of ET in plasma, urine, or cervical smears. Within the ET/ETR system, ETR-A is selectively up-regulated in placental tissue of delayed miscarriages as compared to normal pregnancies. ETR protein processing is similar in both groups.

[Influence of single leaf Asarum himalaicum on renal function of rabbits].

OBJECTIVE: To study the influence of single leaf Asarum himalaicum on the renal function of rabbits. METHODS: Rabbits were divided into three groups. Asarum himalaicum, Asarum heterotropoides and normal saline were intravenously administered to the rabbits of one group respectively. The urine volume per minute, urine pH, urine glucose, protein and red blood cells, BUN, SCr, TXB2, 6-keto-PGF1alpha, TXB2/6-keto-PGF1alpha, endothelin, p-aminohippuric acid clearance rate and phenolsulfonphthalein excretion rate were tested before and after the administration. RESULTS: A certain dosage of single leaf Asarum himalaicum caused acute renal failure in rabbits. The indices tested were significantly different between rabbits administered Asarum himalaicum and normal saline. As compared with the rabbits administered Asarum heterotropoides, the results of indices tested decreased, but without statistical significance, except for SCr. CONCLUSION: The single leaf Asarum himalaicum can cause renal damage to rabbits. Its renal toxicity is lower that that of Asarum heterotropoides.

ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats.

We hypothesize that endothelin-A receptor stimulation contributes to the elevated blood pressure and superoxide production in endothelin-B receptor-deficient rats on a high salt diet. Experiments were conducted on homozygous endothelin-B-deficient (sl/sl) and wild-type rats (wt) fed a high salt diet (8% NaCl) for 3 weeks. Separate groups were given normal drinking water or water containing the endothelin-A receptor antagonist, ABT-627 (5 mg/kg per day; n = 8-9 in all groups). On a normal salt diet, (sl/sl) rats had a significantly elevated systolic blood pressure compared with wt (138 +/- 3 vs 117 +/- 4 mmHg, respectively; P < 0.05). High salt diet caused a significant increase in systolic blood pressure in (sl/sl) rats compared with wt (158 +/- 2 vs 138 +/- 3 mmHg, respectively; P < 0.05). Endothelin-A receptor blockade decreased systolic blood pressure in (sl/sl) rats on high salt (125 +/- 5 mmHg; P < 0.05 vs without antagonist) without affecting the systolic blood pressure in wt (119 +/- 4 mmHg). Aortic superoxide production (lucigenin chemiluminescence) and plasma 8-isoprostane were elevated in sl/sl rats and were significantly reduced by endothelin-A receptor blockade in sl/sl, but not in wt rats. These findings suggest that endothelin-1, through the endothelin-A receptor, contributes to salt-induced hypertension and vascular superoxide production in endothelin-B-deficient rats.

Gender differences in ET and NOS systems in ETB receptor-deficient rats: effect of a high salt diet.

The purpose of this study was to determine if rats lacking the ETB receptor have altered renal endothelin (ET) production and NO synthase (NOS) activity in response to high salt and if female rats are better able to control blood pressure through higher NOS activity in rats heterozygous (sl/+) and homozygous (sl/sl) for ETB receptor deficiency. On normal salt (0.4% NaCl; NS), male sl/sl rats had higher systolic blood pressures compared with male sl/+ and female sl/+ and sl/sl rats. On a high salt diet (10% NaCl; HS), blood pressure in male sl/+ rats was significantly higher than female sl/+ rats. However, ETB receptor deficiency caused much larger increases in blood pressure in male and female rats. On NS, urinary ET excretion was not different between male and female of either genotype. HS significantly increased ET excretion in male and female sl/+ rats, but the increase was significantly less in sl/sl compared with sl/+. Homogenates of inner medullary collecting duct tissue were separated into particulate and cytosolic fractions and total NOS activity measured by conversion of [3H]L-arginine to [3H]L-citrulline. Female rats had significantly greater cytosolic NOS activity compared with male rats on NS. On HS, cytosolic NOS activity was lower in all groups compared with NS rats, whereas particulate NOS activity was significantly greater in male and female sl/+ rats compared with male and female sl/sl rats. These data support our hypothesis that NOS protects against rises in blood pressure in female rats and ETB receptors prevent further increases in blood pressure due to increases in renal ET production and NOS activity.

Infusion of radiocontrast agents induces exaggerated release of urinary endothelin in patients with impaired renal function.

BACKGROUND: The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure. METHODS: We measured plasma endothelin-1 (ET) and the urinary excretion of endothelin-like immunoreactivity before and after infusion of radio contrast medium (CM) in patients with normal renal function (group N; n = 6; mean serum creatinine concentration, 0.8 +/- 0.1 (SEM) mg/dl), and in another group, with renal dysfunction (group R; n = 6; 2.7 +/- 0.5 mg/dl). Half-normal saline (0.45% NaCl solution) was continuously infused in all patients for 25 h, at a rate of 100 ml/h; starting from 5 h before the infusion of CM. RESULTS: Plasma ET in group R (5.2 +/- 1.4 pg/ml) was significantly higher than in group N (0.9 +/- 0.3; P << 0.01). Urinary endothelin excretion corrected by creatinine concentration (uET/Cr) in group R (7.9 +/- 2.4 mg/g Cr) was significantly higher than in group N (1.5 +/- 0.4 mg/g Cr; P << 0.05). Urinary excretion levels of N-acetyl-Beta- d-glucosaminidase (NAG) and Beta2-microglobulin (Beta2M) were also significantly higher in group R (0.8 +/- 0.2 mU/g Cr and 670 +/- 400 mg/g Cr, respectively) than in group N (0.3 +/- 0.1 and 7.5 +/- 2.2, respectively). After CM infusion, uET/Cr in group R significantly increased, to 10.7 +/- 2.6 mg/g Cr on the next day and returned to baseline level on the third day. NAG and Beta2M showed a similar pattern, but a significant change in NAG was observed on the second day in group R. In group N, uET/Cr, NAG, and Beta2M did not change after CM infusion. Plasma ET remained unchanged throughout the observation period of 4 days in both groups. No patient developed pulmonary edema or a significant rise in serum creatinine (more than 0.5 mg/dl), caused by infusion of the amount of half-normal saline used. CONCLUSIONS: In the present study, uET/Cr increased after the administration of CM only in the patients with renal impairment. This difference in endothelin reaction may be a causal one, in that patients with renal insufficiency readily develop RCN. The infusion of half-normal saline starting before CM infusion causes no side effects and is safe for the prevention of CM-induced acute renal failure. The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.

Endothelins and markers of renal damage in recently diagnosed hypertensive patients.

Endothelin has been identified as a potent vasoconstrictor. The aim of this study was to evaluate urinary endothelins and their relation to other markers of renal damage, such as microalbuminuria, creatinine, and N-acetyl-beta-glucosaminidase (NAG), in a group of recently diagnosed (less than 1 year) hypertensive subjects and a control group. We selected 50 subjects and divided them into two groups: 27 hypertensive patients (15 females and 12 males) without previous pharmacologic therapy, and 23 healthy, normotensive subjects (12 females and 11 males). All patients underwent a history and physical examination, chest x-ray, electrocardiography, funduscopy, and hematologic and biochemical analyses. Endothelins, microalbuminuria, creatinine, and NAG values were also determined in 24-hour urine samples. Creatinine, microalbuminuria, and NAG values were found to be higher in hypertensive than in normotensive subjects. The hypertensive group showed a nonsignificant elevation of total endothelin. In conclusion, the determination of elevated urinary endothelin does not appear to be an early marker of organ damage in hypertensive subjects. The urinary excretion of protein, creatinine, and NAG was higher in hypertensive subjects. A positive correlation was found between the urinary excretion of endothelins and markers of renal damage, microalbuminuria and NAG values. The relationship between endothelins and hypertension was without statistical significance.

Interaction of the endothelin system and calcineurin inhibitors after kidney transplantation.

Plasma endothelin (ET)-1 concentrations have been shown to be elevated in patients receiving calcineurin-inhibitors (CI). We investigated urinary and plasma ET-1 (uET-1, pET-1), BigET-1 (uBigET-1, pBigET-1) concentrations, and plasma soluble endothelin-converting enzyme (ECE) concentrations in 381 adult caucasian kidney allograft recipients with graft survival of more than 2 years from the outpatients department of our clinic. Blood and urine probes were always drawn immediately before morning dosage of immunosuppressants. Mean of urinary protein excretion (meanProt) and mean of serum creatinine (meanCrea) were calculated from all available measurements in the most recent year. uET-1 and uBigET-1 were adjusted for urinary protein excretion by calculating uET-1/meanProt and uBigET-1/meanProt. Patients (n=310) were on a cyclosporine A or FK506 (CI-group) based immunosuppression protocol, and 71 patients were immunosuppressed without use of CI (nonCI group). Time since transplantation was similar in both groups (mean+/-S.D.; CI-group: 7.55+/-2.50; nonCI-group: 7.74+/-3.06 years, P=0.240) as well as meanCrea (mean+/-S.D.; CI-group: 1.97+/-1.34; nonCI-group: 1.77+/-1.29 mg/dl, P=0.326). pET-1 was significantly higher in the CI-group, compared with nonCI (mean+/-S.D.; 0.87+/-1.4 versus 0.56+/-0.76 fmol/ml, P=0.011). pBigET-1 was similar (mean+/-S.D.; 0.85+/-1.41 versus 0.70+/-1.21 fmol/ml, P=0.33). ECE concentrations were higher in the CI group (mean+/-S.D.; 14.30+/-18.02 versus 9.23+/-7.42 ng/ml, P=0.001). uET-1/meanProt and uBigET-1/meanProt concentration were similar in the CI-group compared with the nonCI-group (mean+/-S.D.; uET-1/meanProt: 15+/-24 versus 21+/-40 pmol/g, P=0.139; uBigET-1/meanProt: 34+/-55 versus 19+/-23pmol/g, P=0.248). pET-1 elevation in patients receiving CI might be more likely to be due to elevated conversion of pBig-ET-1 by more ECE, and not to higher concentrations of pBigET-1.

Renal endothelin in chronic angiotensin II hypertension.

To determine the influence of chronic ANG II infusion on urinary, plasma, and renal tissue levels of immunoreactive endothelin (ET), ANG II (65 ng/min) or saline vehicle was delivered via osmotic minipump in male Sprague-Dawley rats given either a high-salt diet (10% NaCl) or normal-salt diet (0.8% NaCl). High-salt diet alone caused a slight but not statistically significant increase (7 +/- 1%) in mean arterial pressure (MAP). MAP was significantly increased in ANG II-infused rats (41 +/- 10%), and the increase in MAP was significantly greater in ANG II rats given a high-salt diet (59 +/- 1%) compared with the increase observed in rats given a high-salt diet alone or ANG II infusion and normal-salt diet. After a 2-wk treatment, urinary excretion of immunoreactive ET was significantly increased by approximately 50% in ANG II-infused animals and by over 250% in rats on high-salt diet, with or without ANG II infusion. ANG II infusion combined with high-salt diet significantly increased immunoreactive ET content in the cortex and outer medulla, but this effect was not observed in other groups. In contrast, high-salt diet, with or without ANG II infusion, significantly decreased immunoreactive ET content within the inner medulla. These data indicate that chronic elevations in ANG II levels and sodium intake differentially affect ET levels within the kidney and provide further support for the hypothesis that the hypertensive effects of ANG II may be due to interaction with the renal ET system.

Evidence for endothelin involvement in the response to high salt.

Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ET(B) receptor, may participate in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk of baseline measurements, rats were given either high (10%) or low (0.08%) NaCl in chow for the remainder of the experiment (n = 5 in each group). MAP was significantly increased in rats on a high-salt diet (115 +/- 2 mmHg) compared with rats on the low-salt diet (103 +/- 2 mmHg; P < 0.05). All rats were then treated with the ET(B) receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg x kg(-1) x day(-1). ET(B) blockade produced an increase in MAP within a few hours of treatment and was significantly higher in rats on the high-salt diet over a 1-wk period (170 +/- 3 vs. 115 +/- 3 mmHg, P < 0.01). To determine whether the increase in MAP during A-192621 treatment was due to increased ET(A) receptor activation, all rats were then given the ET(A)-selective antagonist ABT-627 in the drinking water while a low-salt/high-salt diet and ET(B) blockade were continued. ABT-627 decreased MAP within a few hours in rats on either the high-salt (113 +/- 3 mmHg) or low-salt (101 +/- 3 mmHg) diet. These results support the hypothesis that endothelin, through the ET(B) receptor, participates in blood pressure regulation in the response to salt loading.

Hemodynamic, renal, and endocrine responses to acute ET(A) blockade at different ANG II plasma levels.

Angiotensin (ANG) II effects may be partly mediated by endothelin (ET)-1. This study analyses the hemodynamic, renal, and hormonal responses of acute ET(A) receptor antagonism (LU-135252) at two ANG II plasma levels in eight conscious dogs. Protocol 1 involved a 60-min baseline, followed by two doses of ANG II for 60 min each (4 and 20 ng. kg(-1). min(-1)), termed ANG II 4 (slightly increased) and ANG II 20 (pathophysiologically increased ANG II plasma concentration). Protocol 2 was the same as protocol 1 but included 15 mg/kg iv LU-135252 after the baseline period. Protocol 3 was a 3-h time control. ANG II without LU-135252 did not increase plasma big ET-1 and ET-1, whereas LU-135252 increased ET-1 transiently after injection. This transient ET-1 increase was not reflected in urinary ET-1 excretion. The ANG II induced decreases in sodium, water, and potassium excretion, glomerular filtration rate, and fractional sodium excretion were not different with and without LU-135252. Mean arterial pressure increased during ANG II and was not lower with LU-135252 (-6 mmHg, not significant). Most importantly, during ANG II 20 LU-135252 prevented the decrease in cardiac output. Simultaneously, systemic vascular resistance increased 40% less, pulmonary vascular resistance was maintained at baseline levels, and central venous and wedge pressure were lower. Because ANG II stimulated endothelin de novo synthesis should just have started after 2 h of ANG II infusion, there must be mechanisms other than blocking the coupling of de novo synthesized endothelins to the ET(A) receptors to explain the effects of acute ET(A) receptor inhibition in our setting.

Endothelial dysfunction in salt-sensitive essential hypertension.

The aim of this study was to evaluate endothelium-dependent and -independent vasodilation, as well as endothelium biochemical markers, in a group of essential hypertensive patients classified on the basis of salt sensitivity. Changes in forearm blood flow in response to acetylcholine, sodium nitroprusside, and N(G)-monomethyl-L-arginine (L-NMMA) infusion were determined by means of strain-gauge plethysmography. Moreover, plasma and urinary concentrations of nitrates, cGMP, and endothelin were measured during low (50 mmol/d) and high (250 mmol/d) salt intake. Salt-sensitive hypertension was diagnosed in 26 patients who exhibited a significant increase in 24-hour mean blood pressure assessed by ambulatory blood pressure monitoring after 1 week of high salt intake. Nineteen patients were considered salt resistant. Compared with salt-resistant hypertensives, salt-sensitive patients presented a significant lower (P=0.005) maximal acetylcholine-induced vasodilation (21+/-6.3 versus 28+/-7.5 mL. 100 mL(-1). tissue. min(-1)). On the contrary, maximal sodium nitroprusside-induced vasodilation did not significantly differ between groups (22.4+/-4.5 versus 23.9+/-5.3 mL. 100 mL(-1). tissue. min(-1)). The decrease in maximal acetylcholine-induced vasodilation promoted by the coadministration of L-NMMA was significantly more pronounced in salt-resistant compared with salt-sensitive patients (P=0.003). Finally, high salt intake promoted a significant decrease in 24-hour urinary nitrate excretion in salt-sensitive patients (from 443+/-54 to 312+/-54 micromol/d; P=0.033) compared with salt-resistant hypertensives (from 341+/-50 to 378+/-54 micromol/d). We conclude that salt-sensitive hypertension is associated with endothelial dysfunction characterized by a defective endothelium-dependent vasodilation. Impairment of the L-arginine-nitric oxide pathway may be responsible for this abnormal endothelial response.

Treatment with a combined endothelin A/B-receptor antagonist does not prevent chronic renal allograft rejection in rats.

A markedly increased expression of endothelin (ET)-1 has been observed in renal allografts with chronic rejection, one of the most common causes of kidney graft loss. In this study we investigated the effect of treatment with a combined ET-A/B-receptor antagonist on the course of chronic renal allograft rejection. Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-to-Lewis isografts and uninephrectomized Lewis rats served as controls. Animals were treated with either the oral combined ET-A/B-receptor antagonist LU224332 (20 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light-microscopic evaluation and immunohistochemical assessment of cell-surface markers. Treatment with LU224332 did not improve survival after 24 weeks (0.47 vs. 0.38; p > 0.05 by log-rank test), nor did it have an influence on blood pressure, creatinine clearance, or proteinuria. Combined ET-A/B-receptor blockade was associated with a reduction of expression of cell-surface markers for macrophages (EDI), T-cells (R73), and major histocompatibility complex (MHC) II (F17-23-2), but did not lead to an improvement of histologic changes of chronic allograft rejection. Our data show that blocking both ET-A- and -B receptors, in opposition to a previously published beneficial effect of selective ET-A blockade, does not prevent the progression of chronic renal allograft rejection and does not prolong survival in this model. Functional integrity of the ET-B receptor therefore seems to play an important role in the nephroprotection provided by selective ET-A-receptor antagonists in chronic renal allograft nephropathy.

Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat kidney.

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/- 6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney (n = 10) did not prevent posttransplantation hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.

Does gender influence human cardiovascular and renal responses to water immersion?

We hypothesized that women and men exhibit similar cardiovascular and renal responses to thermoneutral water immersion (WI) to the neck. Ten women and nine men underwent two sessions in random order: 1) seated nonimmersed for 5.5 h (control) and 2) WI for 3 h, with subjects seated nonimmersed for 1.5 h pre- and 1 h postimmersion. We measured left atrial diameter, heart rate, arterial pressure, urine volume and osmolality, and urinary endothelin, urodilatin, sodium, and potassium excretion. No significant difference existed between groups in cardiovascular responses. The groups also exhibited mostly similar renal responses to immersion after adjustment for body mass. However, female urodilatin excretion per kilogram during immersion was over twofold that of men, and the female kaliuretic response to immersion was delayed and less pronounced relative to that in men. Men may excrete more potassium than women during immersion because men possess greater lean body mass (potassium per kilogram). Results obtained in men during WI may be cautiously extrapolated to women, yet urodilatin and potassium responses exhibit gender differences.

Improved recovery following posttransplant acute renal failure in rat renal isografts with an oral endothelin-A receptor antagonist.

BACKGROUND: Delayed renal function after transplantation is a strong predictor of long-term graft survival. As an increased expression of endothelin (ET) has been demonstrated during ischemia/reperfusion injury, we hypothesized that ET-A receptor blockade could improve the recovery of acute renal failure in a rat model of isogeneic kidney transplantation. METHODS: Kidneys of Fisher (F344, RT1(1v1)) rat donors flushed with cooled University of Wisconsin solution were transplanted into bilaterally nephrectomized Fisher rats. Recipient animals were treated orally either with vehicle or the selective ET-A receptor antagonist LU135252 (30 mg/kg/day p.o.) for 14 days. Unilaterally nephrectomized Fisher rats not subjected to ischemia served as controls. No immunosuppression was given. On days 2, 6 and 14, metabolic studies were performed to evaluate endogenous creatinine clearance, fractional sodium excretion, and urinary endothelin excretion. Kidneys were harvested at the end of the experiment for determination of renal ET content and immunohistochemical assessment. RESULTS: Urinary ET excretion was increased in vehicle-treated isografts compared to uninephrectomized controls after 14 days. Treatment with LU135252 resulted in a significant improvement in creatinine clearance and fractional sodium excretion to the level of uninephrectomized rats after 14 days. Isografts treated with selective ET-A receptor blockade demonstrated a marked reduction in cell surface markers for macrophages/monocytes, T cells, MHC-II, and ICAM-1. CONCLUSION: Treatment with the selective ET-A receptor antagonist LU135252 accelerates recovery of renal function after isogeneic renal transplantation and attenuates cellular graft infiltration. This effect could have major implications for the treatment of patients undergoing renal transplantation, as an improved initial renal function may delay the onset of chronic allograft rejection.

Increased urinary excretion of endothelin during hypothermic perfusion preservation in kidneys subjected to preretrieval warm ischemic injury.

The purpose of the study was two-fold: 1) to determine whether endothelin (ET) levels could be detected in the ureteral effluent during hypothermic perfusion preservation (HPP) and; 2) to determine whether preretrieval warm ischemic (WI) injury is associated with increased ureteral excretion of ET. In situ pre-WI injury was induced in Lewis rats (n=10) by a 30-min extrinsic occlusion of the suprarenal aorta. The left kidney underwent 16 hr of HPP, and ureteral effluent (UE) from ischemic and control kidneys (n=10) was collected over 16 hr of HPP. The UE ET concentration and total ET excretion over 16 hr of HPP were significantly higher in kidneys subjected to pre-WI injury compared with nonischemic controls. Kidneys subjected to pre-WI injury can be distinguished from nonischemic control kidneys during HPP by a significantly higher concentration of ET in the UE and a higher overall excretion of ET during HPP.

"White coat hypertension" in adolescents: increased values of urinary cortisol and endothelin.

OBJECTIVE: To investigate whether "white coat hypertension" (WCH) in adolescents is an innocent phenomenon or is associated with early changes of the vascular system and/or increased stress response, reflected in the urinary endothelin and cortisol values, respectively. STUDY DESIGN: The study group included 36 subjects, 14 with WCH (8 males and 6 females) aged 12.9 +/- 3 years and 22 normotensive control subjects (12 males and 10 females) aged 13 +/- 3.5 years. WCH was defined as systolic and/or diastolic blood pressure (BP) > or =95th percentile for age, sex, and height and with reported normal BP measurements at home. Urinary endothelin (UET1), urinary free cortisol (UFC), and plasma renin levels were determined by radioimmunoassay; and urinary albumin levels were determined by nephelometry. For statistical analysis, the Mann Whitney U test, Spearman correlation coefficient, and multivariate analysis of variance/multivariate analysis of covariance were used, as applicable. RESULTS: The 24-hour values of UET1 and UFC were greater in male subjects with WCH than in male control subjects (P =.02), whereas no such difference was found in female subjects. The difference in UFC values in male subjects was accounted for by the day values. In subjects with WCH, and not in control subjects, a positive correlation of UET1 to UFC (r = 0.59, P =.027), diastolic BP (r = 0.55, P =.04), and mean BP (r = 0.65, P =.012) was detected. CONCLUSIONS: Our data indicate that WCH in adolescence may not be an innocent phenomenon and may represent a prelude to permanent idiopathic hypertension of adulthood.

Renal glomerular response to the inhibition of prostaglandin E2 synthesis and protein loading after the relief of unilateral ureteropelvic junction obstruction.

PURPOSE: We investigated glomerular filtration rate and renal function reserve after the surgical relief of partial obstruction. MATERIALS AND METHODS: We evaluated 4 boys and 1 girl 9 to 14 years old who underwent pyeloplasty because of unilateral ureteropelvic junction obstruction. Contralateral normal kidneys served as controls. The glomerular filtration rate (inulin clearance), and urinary excretion of prostaglandin E2, thromboxane B2 and endothelin were determined at baseline and after a meal of 4 gm./kg. cooked unsalted red meat on day 4 postoperatively. Tests were repeated the following day 1 hour after the oral administration of 20 mg./kg. aspirin, an inhibitor of prostaglandin E2 synthesis. Urine was collected separately through a bladder catheter and another catheter placed in the upper renal pelvis at surgery. RESULTS: Glomerular filtration rate at baseline was significantly greater in normal than in surgically treated kidneys (77.2 ml. per minute, range 60 to 98 versus 63.6, range 43 to 78, p = 0.04). Aspirin did not change baseline inulin clearance in normal kidneys but it significantly decreased the glomerular filtration rate in operated renal units (-4% versus -26.4%, p = 0.04). The concentration of all vasoactive compounds was not significantly different in the urine specimens of normal and operated kidneys. The administration of aspirin resulted in a significant decrease in mean urinary prostaglandin E2 excretion plus or minus standard error in operated but not in normal renal units (0.64+/-0.12 ng. per minute versus 0.27+/-0.06, p = 0.04). When expressed as mean versus baseline values, protein induced glomerular hyperfiltration seemed lower in operated than in contralateral intact kidneys (6.9% and 12.4%, respectively). CONCLUSIONS: In the immediate postoperative period previously obstructed kidneys maintain renal function via mechanisms that depend on the activation of prostaglandin, mimicking normal renal function. This effect is decreased by drugs that inhibit prostaglandin E2 production. Therefore, renal damage may be present when the glomerular filtration rate appears normal.