Relationship between deficiency of vitamin D and exponents of metabolic syndrome.

OBJECTIVE: Widespread hypovitaminosis D and an increased incidence of metabolic syndrome (MetS) represent significant problems of contemporary medicine but link between them remain unresolved. We aimed to define relationship between vitamin D serum concentration and exponents of MetS. PATIENTS AND METHODS: The studies were conducted on 70 individuals (51 with and 19 without MetS). Concentrations of 25(OH)D (25-hydroxyergocalciferol and 25-hydroxycholecalciferol), calcium, cholesterol, HDL, cholesterol LDL, triglycerides, fasting glucose, blood pressure and anthropometric parameters were measured. RESULTS: Median concentration of vitamin D in the research population amounted to 41.46 nmol/L. Concentration of 25(OH)D in MetS group was lower than in remainder participants (38.45 nmol/L vs. 58.50 nmol/L, p = 0.0104). An inverse correlation was demonstrated between 25(OH)D level on one hand and body weight, waist and hips circumference, adipose body weight, Body Mass Index, Waist to Height Ratio (WHtR), glycaemia and number of MetS components on the other in persons free of MetS. No such relationships could be documented in MetS group. In the entire population values of Waist to Hip Ratio (WHpR) and WHtR indices manifested correlation with hyperglycaemia, hypertriglyceridaemia, low HDL concentrations. CONCLUSIONS: In persons without MetS a relationship was detected between vitamin D concentration and exponents of metabolic syndrome, although further studies on this problem are required.

Plasma ghrelin and interleukin-6 levels correlate with body mass index and arterial blood pressure in males with essential hypertension.

We examined an association between ghrelin, including its major isoforms, interleukin-6 (IL-6), body mass index (BMI), and mean arterial pressure (MAP) in male overweight patients with essential hypertension. Twenty hypertensive male patients with newly diagnosed essential hypertension (EH) before starting drug treatment and 22 age-matched healthy controls were enrolled in the study. Fasting total plasma ghrelin (TGhr), acyl ghrelin (AGhr), des-acyl ghrelin (DGhr) and IL-6 were determined and correlations between studied parameters were calculated. We found significantly lower total plasma ghrelin and higher plasma IL-6 in hypertensives when compared with the control. In patients with hypertension the negative correlations were found: between TGhr and BMI, DGhr and BMI, TGhr and MAP, and between DGhr and MAP. IL-6 positively correlated with BMI and MAP in hypertensive subjects. No correlations between all forms of ghrelin and IL-6 were noted. The changes in plasma ghrelin and IL-6 contribute independently to the elevated blood pressure in essential hypertension. Negative correlation of DGhr and MAP may suggest its hemodynamic involvement in regulation of blood pressure.

The influence of antihypertensive drugs on mineral status in hypertensive patients.

OBJECTIVES: Long-term therapy of hypertension may influence mineral status in patients. However, drug-micronutrient interactions are largely unexplored in practice. This study intended to evaluate the effect of hypotensive monotherapy on iron, zinc, and copper levels, as well as on selected biochemical parameters, in newly diagnosed patients with hypertension, and to assess the influence of diet with optimal mineral levels on the mineral balance in these subjects. PATIENTS AND METHODS: Forty-five patients, aged 18-65 years with diagnosed essential hypertension, beginning monotherapy treatment with diuretics, calcium antagonists, angiotensin-converting enzyme inhibitors, and ß-blockers, were employed. Over three months, the patients underwent monotherapy (stage II). Next, patients were randomly divided into a diet group (of 27 subjects) and a control group (of 18 subjects). In this stage, which lasted one month, patients were given the same drug but also followed an optimal mineral-content diet (for the diet group), or else continued drug use without any change in diet (for control group) (stage III). Lipids, glucose, ceruloplasmin, and ferritin--along with superoxide dismutase and catalase activities--were assayed in serum. Iron, zinc, and copper concentrations in serum, erythrocytes, and urine were determined using flame atomic absorption spectrometry. Blood pressure was measured. Diet intake was monitored at each stage. RESULTS: It was found that the zinc level in serum significantly decreased following treatment, and that the use of the optimal-mineral diet during antihypertensive treatment markedly increased zinc serum concentration. After treatment, a significant increase in zinc excretion in the urine was observed. Glucose levels in the serum of patients in stage II were significantly higher than in the baseline. In patients in the diet group, glucose levels markedly decreased. Moreover, a negative correlation was found between serum glucose and zinc levels in patients. CONCLUSIONS: Antihypertensive treatments should include monitoring of mineral status. It seems that the zinc balance of patients on long-term therapy with hypotensive drugs may benefit from an optimal-mineral diet.

Evaluation of insulin resistance, tumor necrosis factor alpha, and total antioxidant status in obese patients smoking cigarettes.

INTRODUCTION AND BACKGROUND: Obesity and smoking are leading causes of morbidity and mortality worldwide. Cross-sectional studies indicate that heavy smoking may be associated with a greater risk of obesity. While there are important unresolved issues in relation to the effect of smoking on body weight, there is increasing evidence that smoking is conducive to a greater accumulation of visceral fat and greater insulin resistance. AIM: of this study was to determine the potential influences of obesity and smoking on tumor necrosis factor alpha (TNF-α), total antioxidant status (TAS), and insulin resistance. SUBJECTS AND METHODS: 30 obese nonsmokers, 30 obese smokers, 30 normal-weight smokers, and 30 healthy volunteers (the control) were studied. In all subjects, assessments of TNF-α, TAS, and insulin were made. Insulin resistance was evaluated according to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol. RESULTS: TNF-α concentrations, as well as insulin resistance levels, in obese patients significantly exceeded those observed in the control. Compared to the control, obese patients presented significantly lower TAS levels. In the group of obese patients who actively smoked cigarettes, further increases in TNF-α and insulin resistance, as well as decreases in TAS level, were noticed. TNF-α concentration and insulin resistance levels were significantly higher, while TAS was lower in normal-weight smoking subjects, compared to the control. A positive correlation between TNF-α and HOMA-IR was found in the overall population. CONCLUSIONS: Obesity may evoke inflammatory processes, oxidative stress, and insulin resistance, all of which are aggravated by cigarette smoking. TNF-α should be considered in the complex pathogenesis of insulin resistance in obese patients who actively smoke.

Supplementation with L-arginine favorably influences plasminogen activator inhibitor type 1 concentration in obese patients. A randomized, double blind trial.

BACKGROUND: Elevated plasminogen activator inhibitor type 1 (PAI 1) plays an important role in the pathogenesis of excess blood coagulability in obese patients. L-arginine supplementation has shown to be associated with enhanced cardiovascular and metabolic health. The aim of the study was to assess the effect of L-arginine supplementation on PAI 1 concentration and to evaluate the relation to changes in nitric oxide (NO) plasma level, insulin sensitivity (M value), and total antioxidant status (TAS) in obese patients. MATERIAL/SUBJECTS AND METHODS: A randomized, double-blind, placebo-controlled study was conducted from March 2010 to June 2011. Eightyeight obese patients were randomly assigned to receive either 9 g of L-arginine or placebo daily for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed, and PAI 1, NO, TAS levels were assessed. Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp technique. RESULTS: We found that 6-month L-arginine supplementation resulted in significant decrease of PAI 1. Significant increase of NO, TAS, and insulin sensitivity level were noticed. In a group of patients treated with L-arginine, negative correlation between a change of insulin sensitivity value and a change of PAI 1 concentration was found. CONCLUSIONS: The present findings demonstrate favorable influence of L-arginine supplementation on PAI 1 concentration in obese patients. Beneficial influence is related to insulin sensitivity improvement. The potential therapeutic role of L-arginine administration in patients with obesity needs further investigation.

Oral L-arginine supplementation in patients with mild arterial hypertension and its effect on plasma level of asymmetric dimethylarginine, L-citruline, L-arginine and antioxidant status.

BACKGROUND: Potential role of L-arginine supplementation as a new effective strategy of improving endothelial function in patients with hypertension is recently under consideration. OBJECTIVE: To evaluate influence of 28-day oral supplementation of L-arginine on plasma level of asymmetric dimethylarginine (ADMA), L-citrulline, L-arginine and total antioxidant status (TAS), in patients with mild arterial hypertension. SUBJECTS AND METHODS: 54 participants (24 women and 30 men) were studied. Ambulatory blood pressure monitoring (ABPM) was used for allotting patients to either healthy control group (19 subjects) or hypertensive treatment group (35 patients). Patients were later randomized to either L-arginine (2 g tid or 4 g tid) or placebo. During 28 days of study on 5 consecutive visits TAS, plasma level of ADMA, L-citrulline, and L-arginine were measured. RESULTS: In patients with mild hypertension treated with L-arginine significant increase in TAS and plasma level of arginine and citrulline was observed. Additionally plasma ADMA concentrations after 28 days of L-arginine supplementation significantly exceeded initial concentrations. CONCLUSIONS: L-arginine supplementation increases plasma arginine, citrulline and TAS in patients with mild arterial hypertension. It confirms the thesis that augmented concentrations of L-arginine stimulate NO biosynthesis which leads to reduction of oxidative stress. Increase of ADMA plasma level after L-arginine supplementation confirms correlation between ADMA and L-arginine.

Serum resistin concentrations are higher in human obesity but independent from insulin resistance.

UNLABELLED: Although obesity may be linked to resistin, the role of resistin in humans is still controversial. Conflicting results of the associations between resistin and BMI and measures of insulin resistance were reported. In view of the yet unexplained role of resistin in human obesity, the aim of this study was to examine correlations between serum resistin concentrations and the degree of human obesity and insulin sensitivity. For this purpose, we investigated 2 homogenous groups of obese and non obese humans, in whom the presence of obesity was the solely differentiating factor. The WHO definition of obesity was used. Study group consisted of 136 obese subjects (75 women and 61 men) and 48 non-obese controls (31 women, 17 men) aged 48.0 ± 10.1, and 48.8 ± 13.4 yrs, respectively. RESULTS: Obese subjects showed higher resistin concentrations than non obese controls (24.89 ± 9.73 ng/mL, median 26.61 vs. 15.34 ± 4.68 ng/mL, median 14.76, P < 0.0001). Resistin concentrations correlated with BMI in the whole cohort (r = 0.4296, P < 0.0001), but not in obese and non-obese subjects separately (r = 0.1418, P = 0.0997; r = 0.2712, P = 0.0623, respectively). Moreover, serum resistin was not influenced by insulin resistance in either group examined. CONCLUSION: Although concentrations of resistin differ between obese and non-obese humans, no relationship between resistin concentration and insulin resistance has been found. Correlations between resistin and BMI are present only in a mixed population but disappear in non obese and obese subjects when analyzed separately.

Leptin, soluble leptin receptors, free leptin index, and their relationship with insulin resistance and BMI: high normal BMI is the threshold for serum leptin increase in humans.

Leptin binds to the soluble form of its receptor (sOB-R). Leptin and sOB-R balance (free leptin index, FLI) reflect leptin activity. Leptin correlates with obesity and insulin resistance, but it remains uncertain whether sOB-R and FLI also do the same. Therefore, the aim of this study was to measure serum leptin, sOB-R, and FLI, and evaluate their associations with BMI and insulin resistance. We studied 145 obese and 49 nonobese humans. Obesity was defined according to WHO (BMI >30 kg/m (2)). Results are given as: median and interquartile range, obese vs. nonobese, respectively. Leptin (ng/ml): 30.83, 37.27 vs. 8.31, 10.04; sOB-R (ng/ml): 17.62, 17.05 vs. 27.25, 11.30; FLI: 231.2, 310.0 vs. 30.85, 27.77; HOMA: 5.99, 6.64 vs. 3.92, 4.52; p<0.001 for all. Serum leptin, sOB-R, and FLI did not correlate with insulin resistance separately in obese and nonobese humans. Leptin and FLI, but not sOB-R, were associated with insulin resistance in obese and nonobese subjects examined together. Leptin, sOB-R and FLI differed between obese and nonobese humans, and, except sOB-R, correlated with BMI. In piecewise linear regression, BMI threshold where leptin increased was 24.6 (r=0.5969, p=0.00016 and <0.00001). Leptin and its free index, but not sOB-R, correlate with BMI only in a mixed obese and nonobese human cohort, and not in isolated obese or nonobese groups. Moreover, BMI threshold where leptin starts to increase is 24.6 kg/m (2), which is lower than the cutoff for overweight. Under the conditions, metabolic abnormalities may occur in parallel to much lower BMI levels as expected so far.

Serum adiponectin concentrations are not related to glycosylated hemoglobin levels (HbA1c) in obese diabetic and non-diabetic caucasians.

UNLABELLED: Although circulating adiponectin has been inversely correlated with obesity, type 2 diabetes and serum glycosylated hemoglobin (HbA1c) in humans, contradictory reports on that subject exist. In this study, serum concentrations of adiponectin in obese non-diabetic and diabetic humans were measured to examine whether they were associated with levels of HbA1c. The WHO definitions of obesity and diabetes were used. One hundred and five obese euglycemic subjects and 49 obese diabetics (aged 51+/-6.9, and 52+/-6.7 years, respectively) were studied. Their BMI, HbA1c and % of body fat were measured. Adiponectin was determined by an enzyme-linked immunosorbent assay. Although the serum adiponectin concentrations differed between diabetics and non-diabetics ( P<0.01), they were not correlated with HbA1c (r=-0.0814; P=0.5823, and r=-0.1861; P=0.1099, for diabetics and non-diabetics, respectively). Both diabetics and non-diabetics were segregated into tertiles according to their HbA1c levels. Plasma adiponectin did not differ significantly between the high (H), intermediate (I), and low (L) HbA1c tertiles. CONCLUSION: Concentrations of adiponectin were not correlated with levels of glycosylated hemoglobin in the diabetic and non-diabetic subjects examined.

Plasma homocysteine is a determinant of tissue necrosis factor-alpha in hypertensive patients.

Chronic sub-clinical inflammation observed in hypertension plays a prominent role in the progression of atherosclerosis. Accumulating evidence suggests that homocysteine (Hcy) can cause inflammation. The aim of this study was to compare the predictive utility of Hcy and lipid measures as determinants of inflammation in hypertensive patients. We studied a group of 100 patients (45.0+/-12.2 years old) with essential hypertension and a control group of 40 healthy volunteers (44.0+/-8.7 years old). We found that plasma total Hcy (tHcy), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP) were significantly higher in hypertensive patients compared with the control group. The subgroup of hypertensive patients with obesity had higher levels of TNF-alpha (p<0.001), IL-6 (p<0.01), and tHcy (p=0.063), compared with the subgroup of hypertensive patients without obesity. The subgroup of patients with a history of myocardial infarction or stroke had significantly higher levels of tHcy, TNF-alpha, IL-6, and CRP compared to patients with a negative history of vascular events. In the group of hypertensive patients, a strong positive correlation between tHcy and TNF-alpha was observed (r=0.48; p<0.001). In contrast, no correlation was observed between TNF-alpha and any of the lipid measures. In multivariate regression analysis tHcy, but not lipids, was an independent predictor of TNF-alpha. In conclusion, our findings show that plasma tHcy is a determinant of TNF-alpha in hypertension and that obesity or a history of vascular events aggravates inflammation in patients with hypertension. A positive correlation between Hcy and TNF-alpha suggests a mechanism underlying the pro-atherogenic properties of Hcy.

The Y111 H (T415C) polymorphism in exon 3 of the gene encoding adiponectin is uncommon in Polish obese patients.

The genetic background of obesity is under research. Obesity-related phenotype candidate genes include the gene encoding adiponectin (AdipoQ). In this study, exon 3 of the adiponectin gene was screened for the Y111 H (Tyr111His, or T415C, rs17366743) polymorphism, and adiponectin serum concentrations were measured in 206 obese subjects (110 women and 96 men, aged 50.5+/-16.9 years). Their BMI, % of body fat, plasma glucose, insulin, and glycosylated hemoglobin were measured. Adiponectin was determined by enzyme-linked immunosorbent assay. Genomic DNA was extracted from peripheral blood leukocytes. A fragment of exon 3 of the adiponectin gene was amplified in PCR and screened for the Y111 H polymorphism in SSCP analysis. Genetic screening revealed a different SSCP pattern in 2 subjects. Subsequent genotyping disclosed the TC genotype in both subjects, resulting in Y111 H heterozygote variant frequency of 0.01 in the whole cohort. Other results for SNP (single nucleotide polymorphism) positive and negative subjects were as follows, respectively: BMI (kg/m (2)) 39.95+/-9.83 vs. 38.12+/-8.56; waist circumference (cm) 122+/-18.4 vs.115+/-16; glucose (mmol/l) 7.51+/-1.86 vs. 5.56+/-0.74; HbA1c (%) 7.55+/-1.86 vs. 6.58+/-1.36; body fat (%) 51+/-2 vs. 44+/-10; plasma insulin (mU/l) 28.92+/-16.50 vs. 37.59+/-47.34; adiponectin (ng/ml) 1301+/-15.8 vs. 5682+/-4156. Due to a proportion of 2 vs. 204, statistical calculations were not possible. The Y111 H adiponectin gene variant is uncommon in Polish obese subjects. Although we observed low adiponectin concentrations in Y111 H SNP heterozygote carriers, this finding was not confirmed by statistics.

Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus.

OBJECTIVE: Leukocyte migration to the subendothelial space is considered crucial in the initiation of atherosclerosis. There is increasing evidence that overexpression of chemokine receptors contribute to this process. CCR5 is one of the receptors present on peripheral T lymphocytes, monocytes and macrophages. We decided to evaluate the expression of CCR5 on monocytes and macrophages in peripheral blood and selected inflammatory markers in patients with type 2 diabetes mellitus before and after the initiation of insulin therapy. MATERIAL AND METHODS: A total of 10 patients with newly diagnosed type 2 diabetes and 6 healthy control subjects were studied. Assessment of CCR5 expression on the surface of monocytes and macrophages in peripheral blood was performed using flow cytometry before the initiation of insulin therapy and after 5-week treatment. Serum concentrations of RANTES, TNF-alpha, IL-6 and hsCRP were assessed. RESULTS: When compared to control subjects, we observed higher densities of CCR5 on the surface of peripheral blood monocytes and macrophages and higher concentrations of RANTES, TNF-alpha, IL-6 and hsCRP before insulin therapy. After 5-week insulin therapy, there was a significant decrease in the expression of CCR5 on the surface of these cells and a significant fall in serum levels of RANTES, IL-6, TNF-alpha and hsCRP. CONCLUSIONS: Type 2 diabetes leads to an increase in the inflammatory process, and insulin therapy inhibits the early stages of this process.

Circulating serum adiponectin concentrations do not differ between obese and non-obese caucasians and are unrelated to insulin sensitivity.

Reduced serum levels of adiponectin in obesity and insulin resistance seem paradoxical, since adipose tissue is the only source of adiponectin, and reports on that subject are contradictory. The aim of this study was to investigate the concentrations of adiponectin in non-obese and obese normoglycemic humans, and to determine the correlation between adiponectin and HOMA index of insulin sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49 non-obese controls (aged 20-55 years) were studied. The serum adiponectin concentrations did not differ between subjects and controls (p=0.6398) and were not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for subjects and controls, respectively). Adiponectin was not correlated with HOMA index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and r=0.0123; p=0.9131, for male subjects and controls, respectively). These results lead to the conclusion that neither the concentrations of adiponectin differ between obese and non-obese humans, nor does any relationship between adiponectin concentration and insulin sensitivity exist.

[The role of rheological factors in the pathogenesis of diabetic nephropathy]. / Rola czynników reologicznych w patogenezie nefropatii cukrzycowej.

In this paper the stages and pathogenesis of diabetic nephropathy have been presented. Factors which influence blood rheology and hemorheologic abnormalities founded in diabetic patients have been reviewed. Attention was paid to the role of rheological parameters in initiating and progression of diabetic nephropathy. The possibilities of prevention of diabetic microvascular complications by influencing blood rheology have been presented.

[Digoxin as a cause of chromatopsia and depression in a patient with heart failure and hyperthyroidism]. / Digoksyna przyczyna objawów barwnego widzenia oraz depresji u chorego z niewydolnoscia serca i nadczynnoscia tarczycy.

67 year old patient with chronic heart failure and persistent atrial fibrillation had overdosed glycosides for several months. The symptoms of gastrointestinal system and nervous system appeared after long term therapy with toxic doses of glycosides. Originally depression was diagnosed based on the central nervous system disturbances. Even though overdose of glycosides was diagnosed the blood serum glycoside level was within the therapeutic limits. Based on the precise analysis of the data, it was concluded that the reason for normal blood serum glycoside level in this case was coexisting hyperthyreosis.

[Leptin and obesity]. / Leptyna a otylosc.

Obesity is associated with increased incidence of cardiovascular diseases, insulin resistance, dyslipoproteinemia and cancer. The discovery of leptin in 1994 has provided a lot of new information about obesity. Leptin is a 167-amino acid peptide synthetized almost exclusively in adipose tissue. This hormone circulates in blood serum in both free and bound forms. The long isoform of leptin receptor is widely distributed in brain, whereas numerous short forms are also being present in peripheral tissues. Leptin acts by binding to the receptors in hypothalamus and altering a release of several neuropeptides, especially neuropeptide Y, regulating energy intake and expenditure. Apart from signaling energy reserves to the brain, leptin promotes hematopoiesis, influences pubertal development and contributes to the increase in arterial blood pressure. Leptin production regulation in humans is poorly understood, but appears to depend on the total body fat, changes in energy intake and serum level of several hormones. Despite the recent advances in the knowledge of both physiology and pathophysiology of leptin, several many important questions require further studies.

Effects of extracorporeal shock wave lithotripsy on renal function in patients with kidney stone disease.

The effects of extracorporeal shock wave lithotripsy on glomerular and tubular renal functions were determined by serum beta2-microglobulin (Sbeta2m) and urinary beta2-microglobulin (Ubeta2m) estimations in patients with nephrolithiasis. Unilateral treatment was performed in all patients. Urinary and serum creatinine levels were determined according to the method of Yatzidis. Sbeta2m and Ubeta2m were measured by radioimmunoassay the day before ESWL, on the day of ESWL, and then 1, 2, 5, 7, 8, 9, 14, and 28 days after treatment. Creatinine clearance, hourly urinary beta2m excretion (Ubeta2m/h), and tubular reabsorption of beta2m (TRbeta2m) were calculated. After lithotripsy, significant increases in Ubeta2m, Ubeta2m/h, and TRbeta2m were found (p < 0.001), whereas Sbeta2m, serum creatinine, and creatinine clearance values remained unchanged. Ubeta2m, Ubeta2m/h, and TRbeta2m reached their pretreatment values within 7-9 days after ESWL. We concluded that ESWL does not affect the glomerular filtration rate; however, it leads to a transient proximal tubular dysfunction.

[Endothelin and arterial hypertension]. / Endotelina a nadcisnienie tetnicze.

Endothelins (ETs) are peptides of 21 amino acids synthesized and released by variety of cells. Endothelin (now this peptide is called endothelin-1 (ET-1)) was isolated and identified in 1988 by Yanagisawa et al. Following studies revealed two other isoforms of endothelin': Endothelin-2 (ET-2) and endothelin-3 (ET-3). All of them bind to two types of receptors (A and B (ET-A r, ET-Br). ET-A r are responsible for concentration mediating. Two subtypes of ET-B r are known. ET-B1 r mediates vasorelaxation; ET-B2 vasoconstriction. ETs (especially ET-1) have variety of biological actions but the most important are vasoconstrictor and mitogenic action. Through these two mechanism ETs may participate in the pathogenesis and/or in the maintenance of hypertension in both experimental animal models and human essential hypertension. The intravenous infusion of synthetic ET induces a long-lasting elevation of blood pressure in experimental animals and in healthy humans. Number of studies have shown enhanced responses to ET in hypertensive subjects but decreased responses have also been reported. Similarly, plasma levels of ET-1 are either normal or elevated in experimental and human essential hypertension. Numerous investigators have suggested an interaction between ET and angiotensin-converting enzyme inhibitors through the renin-angiotensin system or through the accumulation of endogenous bradykinin. Also calcium antagonists of different classes prevent endothelin-induced contractions. Endothelin- converting enzyme inhibitor (phosphoramidon) and ET-A/B r antagonists (bosentan, BQ-123, FR139317) may have potential role as vasodilators in the treatment of hypertension.