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The 'programming hypothesis' proposes that an adverse perinatal milieu leads to adaptation that translates into cardiovascular disease in adulthood. The balance between nitric oxide (NO) and reactive oxygen species (ROS) is disturbed in cardiovascular diseases, including hypertension. Conceivably, this balance is also disturbed in pregnancy, altering the fetal environment; however, effects of perinatal manipulation of NO and ROS on adult blood pressure (BP) are unknown. In spontaneously hypertensive rats (SHR), NO availability is decreased and ROS are increased compared with normotensive Wistar-Kyoto rats, and, despite the genetic predisposition, the perinatal environment can modulate adult BP. Our hypothesis is that a disturbed NO-ROS balance in the SHR dam persistently affects BP in her offspring. Dietary supplements, which support NO formation and scavenge ROS, administered during pregnancy and lactation resulted in persistently lower BP for up to 48 wk in SLIP, offspring. The NO donor molsidomine and the superoxide dismutase mimic tempol-induced comparable effects. Specific inhibition of inducible nitric oxide synthase (NOS) reduces BP in adult SHR, suggesting that inducible NOS is predominantly a source of ROS in SHR. Indeed, inducible NOS inhibition in SHR dams persistently reduced BP in adult offspring. Persistent reductions in BP were accompanied by prevention of proteinuria in aged SHR. We propose that in SHR the known increase in ANG II type 1 receptor density during development leads to superoxide production, which enhances inducible NOS activity. The relative shortage of substrate and cofactors leads to uncoupling of inducible NOS, resulting in superoxide production, activating transcription factors that subsequently again increase inducible NOS expression. This vicious circle probably is perpetuated into adult life. spontaneously hypertensive rat; nitric oxide; inducible nitric oxide synthase; molsidomine; tempol; proteinuria

In the spontaneously hypertensive rat (SHR), renal blood flow (RBF) has been reported to be very dependent on nitric oxide (NO); however, autoregulation is normal, albeit shifted to higher perfusion pressures. To test the hypothesis that in the SHR NO dependency of RBF autoregulation is diminished, we investigated RBF autoregulation in anesthetized young male SHR and normotensive Wistar-Kyoto (WKY) rats before and during acute intravenous NO synthase (NOS) inhibition with [N.sup.[omega]]-nitro-L-arginine (L-NNA) and urinary excretion of nitrate plus nitrite ([U.sub.NOx]V) at different renal perfusion pressures (RPP). Under baseline conditions, SHR had higher mean arterial pressure (147 [+ or -] 4 mmHg) and renal vascular resistance (16 [+ or -] 1 U) than WKY (105 [+ or -] 4 mmHg and 10 [+ or -] 0.5 U, respectively, P < 0.05). RBF was similar (9.4 [+ or -] 0.5 vs. 10.3 [+ or -] 0.1 ml * [min.sup.-1] * g kidney [wt.sup.-1]). Acute NOS blockade increased mean arterial pressure similarly, but there was significantly more reduction in RBF and hence an enhanced increase in renal vascular resistance in SHR (to 36 [+ or -] 3 vs. 17 [+ or -] 1 U in WKY, P < 0.001). The renal vasculature of SHR is thus strongly dependent on NO in maintaining basal RBF. The lower limit of autoregulation was higher in SHR than WKY in the baseline situation (85 [+ or -] 3 vs. 71 [+ or -] 2 mmHg, P < 0.05). Acute L-NNA administration did not decrease the lower limit in the SHR (to 81 [+ or -] 3 mmHg, not significant) and decreased the lower limit to 63 [+ or -] 2 mmHg (P < 0.05) in the WKY. The degree of compensation as a measure of autoregulatory efficiency attained at spontaneous perfusion pressures was comparable in SHR vs. WKY but with a shift of the curve toward higher perfusion pressures in SHR. Acute NOS blockade only increased the degree of compensation in WKY. Remarkably, [U.sub.NOx]V was significantly lower at spontaneous RPP in SHR. After reduction of RPP, the observed decrease in [U.sub.NOx]V was significantly more pronounced in WKY than in SHR. In conclusion, the renal circulation in SHR is dependent on high levels of NO; however, the capacity to modulate NO in response to RPP-induced changes in shear stress seems to be limited. urinary excretion; renal perfusion pressures

Context:Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies). Objective:To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up. Methods:We registered 46 HD patients’ baseline characteristics, mortality and CVE for 108 months. Results: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality. Conclusion:The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up. [ABSTRACT FROM PUBLISHER]

Background and aims. Cardiovascular (CV) disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Kidney disease is associated with increased oxidative stress (OS), a nontraditional CV risk factor. Few studies evaluate the effect of OS markers on CV events (CVE) and survival in HD patients. The aim of this study is to examine potential determinants of OS markers and their predictive role on survival and CV morbidity and mortality in HD patients during a long-term follow-up (108 months). Methods. We conducted an analytical cross-sectional prospective observational study, carried on a cohort of randomly selected HD patients. We registered in 44 HD patients baseline characteristics, OS markers, mortality and CVE over a period of 108 months and we used statistical analysis (descriptive, Kaplan-Meier, univariate and multivariate Cox model) for interpretation. Results. Bound malondialdehyde (bMDA) was positively correlated with serum calcium, protein carbonyls (PC) were inversely correlated with diastolic blood pressure (DBP) and directly correlated with ferritin, NOx was directly correlated with ceruloplasmin) and serum albumin. Of the measured OS markers only bMDA was related to survival (HR=3.29 95% CI (1.28-8.44), p=0.01), and approached statistical significance in the effect on CV mortality (HR=2.85 95% CI (0.88-9.22), p=0.07). None of the measured OS markers was associated with CVE. Conclusions. bMDA has a strong predictive value on survival in HD patients in a long-term follow-up (9 years). Its value is correlated with CV mortality but is not a predictor of CV events. Regular assessment of MDA in HD patients and the development of strategies aimed at reducing oxidative stress in these patients might be beneficial. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction (ED) is marker of atherosclerosis in chronic renal failure. In uremia, visfatin was associated with inflammation and endothelial dysfunction. Materials and methods: We evaluated 32 chronic hemodialysis patients (group 1), divided in 2 subgroups (with and without diabetes mellitus) and 20 volunteers-control group (group 2). Plasma visfatin, endothelial-dependent flow-mediated vasodilatation and nitroglycerin-induced endothelium independent vasodilatation (NMD) were assessed for all groups. Malondialdehyde (MDA), hemoglobin, Kt/V, parathormone, C-reactive protein (CRP), albumin, ferritin, transferin saturation, cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, calcium, phosphorus and body mass index (BMI) were determined in group 1. Results: FMD (p=0.02) and NMD (p=0.01) were significantly higher in group 2 than in group 1. In group 1, FMD negatively correlated with visfatin (p=0.007) and MDA (=0.03) and positively correlated with LDL-cholesterol (p=0.0007). BMI, CRP and HDL-cholesterol were significantly higher (p=0.009, =0.001, =0.01 respectively) in diabetes patients compared to patients with no diabetes, while NMD, albumin and calcium were significantly lower (p=0.04, =0.003, =0.04 respectively). Conclusions: Endothelial dysfunction, measured by FMD, is increased in HD patients compared to controls and is associated with visfatin and oxidative stress. Diabetes mellitus is associated with NMD, but it does not influence FMD and visfatin, even if inflammation is enhanced in these patients. [ABSTRACT FROM AUTHOR]

Calciphylaxis is a life-threatening complication of hemodialysis involving calcium deposition in media of hypodermic arteries and skin necrosis. With current unsatisfactory treatment, the calcium chelator and antioxidant sodium th iosulphate emerges as a possible new therapy. We report the case of a dialysis patient with parathyroidectomy for secondary hyperparathyroidism complicated by severe hypoparathyroidism and hypocalcemia, requiring sustained Ca and vitamin D treatment. With in a year, typical calciphylaxis developed on the breasts, associated with extensive calcification of medium-sized arteries on mammography. Cessation of calcium load and aggressive wound care led to no improvement. Sodium th iosulphate 25g th rice weekly for 2 month s resulted in dramatic healing. Besides unusual location on the breasts, onset of lesions in the setting of an adynamic bone is noteworthy and probably favored by calcium load. This is, to our knowledge, the first use of sodium th iosulphate in calciphylaxis associated to low bone turnover, a valuable therapeutic asset since unlike in hyperparathyroidism, other treatment options lack. Also th is is the first use of sodium th iosulphate for treatment of calciphylaxis in Romania, the drug being prepared in our University. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of mortality in hemodialysis patients. Carotid and cardiac ultrasonographic abnormalities are the rule in these patients. The aim of this study is to evaluate the interrelation between these changes and cardiovascular risk factors in our patients. In 54 stable chronic hemodialysis patients current demographic and biochemical parameters were recorded. Ultrasonographic measurement of intima-media thickness, diastolic diameter of common carotid artery, evaluation of carotid atherosclerotic plaques and transthoracic ecocardiography with evaluation of left ventricular mass index and valvular calcifications were performed, and correlated with cardiovascular risk factors. We found a high frequency of ultrasonographic abnormalities. Remarkably, nontraditional cardiovascular risk factors such as malnutrition, anemia and calcium-phosphate imbalance seem more important than traditional risk factors such as age, gender, smoking, diabetes mellitus, arterial hypertension or obesity for these ultrasonographic changes in hemodialysis patients. [ABSTRACT FROM AUTHOR]

We studied the incidence, risk factors, presentation, treatment and prognosis of calcific uremic arteriolopathy (CUA) in 140 of our hemodialysis patients. Methods. Patients with CUA in the past 3 years have been compared to controls in a cross-sectional survey of 140 hemodialysis patients. Results. Prevalence of CUA was 6/140 (4.28%); common presentation was ulcerated acral necrosis. Age, sex ratio, BMI, prevalence of diabetes were similar in case (n=6) and control (n=134) patients. CUA patients had higher serum calcium (9.58±1.25 mg/dL vs. 8.50±1.03 mg/dL, p=0.01), calcium-phosphate product (71.06±19.67 mg2/dL2 vs. 58.73±17.20 mg2/dL2, p=0.01) and parathormone levels (1854±1407 pg/mL vs. 654±776 pg/mL, p=0.0002). Differences in ingestion of calcium, active vitamin D and non-calcium containing phosphate binders in the year prior to the assessment were not significant. CUA patients had higher CRP values in the 6 preceding months than non CUA patients (6.61±9.68 mg/dL vs. 1.97±4.20 mg/dL, p=0.01); logistic regression disclosed CRP as the only predictive factor for CUA (p=0.03). 4 (66%) of the CUA patients died due to sepsis, as compared to 3(2.23%) of the control group (p=0.001). 2 of 3 parathyroidectomised patients survived. In conclusion, this is, to our knowledge, the first series of CUA reported from Eastern Europe. In our center acral, ulcerated forms of CUA in patients with severe hyperparathyroidism are predominant. [ABSTRACT FROM AUTHOR]

Background: Adiponectin, an insulin-sensitizing, anti-inflammatory and antiatherogenic adipokine, seems to conserve its protective effect against cardiovascular complications in dialysis patients. In diabetic dialysis patients however results are less consistent, higher adiponectin levels being associated with mortality. We intend to study the prognostic value of plasma adiponectin for atherosclerotic complications and all-cause mortality in type 2 diabetic patients on hemodialysis in a multicenter trial; we hereby present our pilot study. Material and methods: All (28) diabetic patients on maintenance hemodialysis in our center were included in the study. History, clinical data, routine laboratory assessment and total plasma adiponectin were obtained. Patients were compared to a control group of 20 nondiabetic hemodialysis patients. During 1 year of follow-up, new occurrence of cardiovascular complications due to atherosclerosis (myocardial infarction and revascularization, amputation or revascularization due to arteriosclerosis obliterans, stroke) and all-cause mortality were recorded. Results: Type 2 diabetic dialysis patients had lower adiponectin levels than dialysis controls (21.08±3.17/ml versus 39.00±10.11μg/ml, p=0.03). In simple regression, adiponectin was correlated to body mass index (r=-0.43, p=0.01) and serum triglycerides (r=-0.62, p=0.0003); in multiple stepwise regression, triglycerides remained the only predictor of plasma adiponectin (p=0.01). Adiponectin levels were higher in women than in men (28.73±5.76 μg/ ml versus 15.33±2.88 μg/ml, p=0.03). There was a statistically significant difference in plasma adiponectin levels between patients with proliferative retinopathy and patients without this condition (27.22±4.87 μg/ ml versus 16.46±3.91 μg/ml, p=0.02). Patients with new onset of cardiovascular events had lower adiponectin levels than controls (12.76±3.52 μg/ml versus 23.34±3.81 μg/ml but the difference did not reach statistical significance, probably due to the small number of patients. Baseline adiponectin was higher in deceased patients than in survivors (29.87±10.32 μg/ml versus 19.61±3.29 μg/ml); again, statistical significance was not reached due to the small cohort. The number of patients to be included in the multicenter trial in order to attain statistical significance for each arm of the above mentioned comparisons was calculated. Conclusions: In diabetic patients treated with hemodialysis, lower adiponectin levels were found in patients with new onset of complications of atherosclerosis, while increased adiponectin might predict all-cause mortality. Further large-scale prospective studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]