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Biomedical subjects

A Hornych

Publications and source records attributed to A Hornych.

At least 19 recordsLinked to original sources
PubMed1995

Effect of ketanserine in cyclosporine-induced renal dysfunction in rats.

Cyclosporine (CsA)-treated female Wistar rats, in dose of 37.5 microM (45 mg)/kg/day for 7 days, exhibited significantly decreased creatinine clearance (Ccr), and provoked body weight loss (BWL), which is consistent with the development of nephrotoxicity (NT). Urine volume (V) did not change and proteinuria (PU) was not provoked. These changes were associated with significantly diminished ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 excretions. Light-microscopic (LM) sections of rat kidneys showed that all kidneys were affected but the lesions (mainly diffuse vacuolization) were reversible. When CsA-treated animals were pretreated with ketanserine (KTS), which antagonizes (a) the direct vasoconstrictor effect of serotonin (5-HT), and (b) the amplifying effects of 5-HT on other vasoactive substances (such as noradrenaline (NA), alpha 1-receptors, histamine, H2 receptors, and prostaglandin F2 alpha), Ccr and urine volume significantly increased, BWL was partially prevented and the ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 excretions were significantly enhanced. LM sections showed that only 5 of 9 rats were affected but the lesions were of less importance. These observations indicate that the NT induced by CsA in our studies was mediated by 5-HT, a potent vasoconstrictor agent, and by the metabolites of arachidonic acid. However, other vasoactive agents and additional mechanisms could also be implicated.

Animals↗
PubMed1995

Normal human polyspecific immunoglobulin G (intravenous immunoglobulin) modulates endothelial cell function in vitro.

We have analysed the in-vitro effect of pooled normal polyspecific immunoglobulin G (IVIg) and F(ab')2 fragments of IVIg on the secretion of prostacyclin (PGI2), thromboxane A2 (TxA2), and endothelin from cultured human umbilical vein endothelial cells. The stable metabolites, 6-keto-PGF1 alpha and TxB2, as well as endothelin, were measured by radioimmunoassay after extraction from the culture supernatants. IVIg inhibited TxB2 and endothelin secretion in a dose-dependent manner, but not that of 6-keto-PGF1 alpha. Therefore the ratio of 6-keto-PGF1 alpha/TxB2 increased (+600%). The effect of F(ab')2 fragments prepared from IVIg was similar to that observed with IVIg, indicating that the effect of IVIg was mediated by the variable region of immunoglobulin. The results suggest that part of the effects of IVIg in inflammatory vasculitis may be due to a modification of the PGI2/TxA2 ratio and inhibition of endothelin secretion, and that natural IgG antibodies may participate in the homeostatic process of endothelium under physiological conditions.

Cells, Cultured↗
PubMed1992

Prostaglandins and systolic blood pressure, but not angiotensin II, independently affect atrial natriuretic peptide levels in man.

1. Two hours after a single dose of indomethacin (INDO), plasma renin activity (PRA) and atrial natriuretic peptide (ANP) levels decreased, which is consistent with an effect of lowering prostaglandins (PG). 2. After 48 h of INDO, PRA remained low but ANP had increased, which is consistent with the known effect of prostaglandin inhibitors to cause sodium retention, with a resulting volume expansion. 3. Infusions of angiotension II (AII), which raises diastolic blood pressure (BP) 20 mmHg or more, consistently raised ANP levels. The ANP response to AII infusion was reduced 48 h after INDO, which is consistent with an important role for PG in AII-stimulated ANP release. 4. After PG were blocked with INDO, the stimulating effect of AII on ANP at doses that increased diastolic BP less than 20 mmHg was insignificant, whereas before INDO it was significant. 5. In dose-response studies, INDO increased the systolic BP response but decreased the ANP response to AII, which is consistent with a direct effect of PG on ANP that is independent of systolic BP. 6. Prostaglandins and BP are important in the ANP response to AII infusion in normal subjects, but AII itself appears to have little direct effect on ANP.

Adult↗
PubMed1991

Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia.

To explore the hypothesis that acute exposure to altitude hypoxia and acute mountain sickness (AMS) are associated with the release of vasoactive eicosanoids, 10 adult subjects were studied at sea-level and after 1-8 days (H1-H8) of exposure to an altitude of 4350 m (Observatoire Vallot). Plasma concentrations of 6 eicosanoids were determined in peripheral venous blood samples by radioimmunoassay after extraction with cooled ethanol and chromatographic separation by HPLC. All subjects experienced symptoms of AMS. Maximal clinical scores were observed at H1 or H2. Symptoms were no longer noted at H8. Hypoxia induced a very large increase in plasma concentration of most eicosanoids; thromboxane B2 (TxB2) and leukotriene B4 (LTB4) were maximum at H1 and H2 (about 5 times the normoxic value); prostaglandins PGE2, 6-keto-PGF1 alpha and PGF2 alpha were maximum at H3 or H4 (about 2.5-5 times of normoxic value). All eicosanoids returned almost to normoxic values by H8. Vasoconstricting mediators were released mostly at the initial phase (H1, H2), vasodilating mediators becoming predominant thereafter (H3, H4). The time pattern of appearance in blood of mediators acting on vascular permeability was strikingly parallel to the clinical score of AMS. In conclusion, exposure to acute hypoxia induced a large increase in plasma concentration of eicosanoids, the variation with time of which is compatible with a hydrostatic-permeability hypothesis of AMS pathophysiology.

Adult↗
PubMed1991

The influence of age on renal prostaglandin synthesis in man.

The purpose of our study was to determine influence of age on renal prostaglandin (PG) synthesis in man. Urinary prostaglandins 6-Keto-PGF1 alpha, TxB2, PGE2 and PGF2 alpha were measured in 45 normotensive subjects aged from 20-95 years. Urinary 6-Keto-PGF1 alpha excretion, reflecting mainly renal cortical prostacyclin synthesis, decreased significantly with age, while urinary TxB2 showed the opposite development. The ratio of urinary 6-Keto-PGF1 alpha/TxB2 decreased with age. PGE2 excretion was preserved in old subjects probably because the age-dependent decrease in renal function concerns mainly the cortex and spares the medulla. PGF2 alpha synthesis was least influenced by age. This age-dependent decrease in renal prostacyclin synthesis may play a role in the renal alterations of the elderly.

Adult↗
PubMed1991

The syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate: is there a deficiency in vasodilator prostaglandins?

1. In Gordon's syndrome (GS; a syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate), excessive proximal sodium reabsorption leads to suppression of renin and aldosterone, hyperkalaemia and hyperchloraemic acidosis. 2. Low urinary levels of vasodilator prostaglandins (PG) have been reported in GS, suggesting renal hypoprostaglandinism as a pathophysiological mechanism. 3. In four cases of GS, levels of vasodilator prostaglandins PGE2 and 6-keto-PGF1 alpha were low. 4. In one case of GS, low PGE2 levels were normalized by dietary salt restriction or diuretic therapy.

Adult↗
PubMed1989

[Reduction of kidney prostaglandin synthesis in patients with essential hypertension. Stimulating effect of cicletanine].

The purpose of this study was to evaluate the level of renal synthesis of vasodilator and natriuretic prostaglandins I2 and E2 in patients with essential hypertension and to test the effect of cicletanine, a new antihypertensive drug, on the renal synthesis of these prostanoids in hypertensive patients. The first part of the study was carried out in 12 healthy normotensive subjects and in 25 patients of both sexes with essential hypertension. The effect of cicletanine administered in dose of 150 mg was assessed in 10 healthy volunteers and 12 hypertensive patients. The urinary levels of prostaglandins 6-keto-PGF1 alpha (a metabolite of prostacyclin PGI2) and PGE2 were measured (HPLC) by radioimmunoassay after extraction and chromatographic separation. In normal subjects the urinary excretion rate of 6-keto-PGF1 alpha was 134 +/- 26 pg/min and that of PGE2 was 180 +/- 25 pg/min. The corresponding values were significantly lower in hypertensive patients. This defect of PGI2 and PGE2 renal synthesis was found in 64 p. 100 and 72 p. 100 respectively of patients with hypertension. Cicletanine increased the urinary excretion of 6-keto-PGF1 alpha by 45 p. 100 and that of PGE2 by 59 p. 100 in hypertensive patients. It also brought to normal limits the secretion of these prostanoids in these subjects. At the dose of 150 mg the drug stimulated natriuresis significantly and increased glomerular filtration in patients with essential hypertension. This renal effect of cicletanine was acutely reduced by the presence of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effects of ciclosporin on plasma renin activity, catecholamines and prostaglandins in patients with idiopathic uveitis.

Animals and humans undergoing treatment with ciclosporin (CS) show a reversible increase in renal vascular resistance and a decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. We evaluated the effects of a 1-week treatment with CS on creatinine clearance, renal arachidonic acid metabolites, plasma renin activity (PRA), plasma aldosterone levels, urinary excretion and plasma levels of catecholamines in 7 patients with idiopathic uveitis. We show that CS treatment induces a significant (p less than 0.05) decrease in creatinine clearance (from 132 +/- 0.5 to 108 +/- 8 ml/min); urinary 6-keto-PGF1 excretion (from 17.8 +/- 4.9 to 10.9 +/- 3.3 ng/mmol creatinine), urinary thromboxane B2 excretion (from 7.0 +/- 1.0 to 3.6 +/- 0.9 ng/mmol creatinine), upright PRA (from 4.2 +/- 0.9 to 2.3 +/- 0.8) and supine PRA (from 2.0 +/- 0.5 to 1.1 +/- 0.3). We found no change in plasma aldosterone levels and plasma levels and urinary excretion of catecholamines. We suggest that the reversible renal vasoconstriction observed in patients treated with CS may be induced by inhibition of renal prostacyclin synthesis. In this setting inhibition of PRA and angiotensin II formation may impair autoregulation of effective filtration pressure and therefore glomerular filtration rate.

Adult↗
PubMed1987

Bartter's syndrome with normal chloride reabsorption during indomethacin treatment.

A 17-year-old male patient with Bartter's syndrome was admitted for renal function studies. This patient had persistent hypokalemia, first found at age 5; the diagnosis of Bartter's syndrome with renal hypersecretion of prostaglandins E2 and F2 alpha had been established at age 13. A congenital defect of chloride reabsorption was expected, but after 4 years of indomethacin treatment no such defect was found. Withdrawal of indomethacin for 1 week resulted in profound hypokalemia and the appearance of a chloride reabsorption defect, with an excessive urinary PGE2 and PGF2 alpha excretion, and a parallel decrease in plasma prostaglandin precursors. The cause of Bartter's syndrome in this patient seems to be renal hyperprostaglandinism.

Adolescent↗
PubMed1986

Acute effects of clometacin on renal prostaglandin biosynthesis in healthy subjects.

In 6 healthy subjects the effect of clometacin on renal function, sodium and water excretion, plasma renin activity and urinary excretion of prostaglandins has been studied. After four days of treatment with clometacin, the excretion of urinary prostaglandins E2, F2 alpha and 6 keto F1 alpha and thromboxane B2 were reduced by 61.2, 41.2, 59 and 42%, respectively. 62% reduction in plasma renin activity was also observed. There was no significant change in mean blood pressure, heart rate, body weight, creatinine clearance or urinary excretion of sodium. It is concluded that clometacin is an efficient cyclooxygenase inhibitor in healthy individuals with a normal sodium intake, and that caution is required when giving clometacin to patients at risk of developing renal failure during treatment with a cyclooxygenase inhibitor.

Adult↗
PubMed1984

[Changes in plasma prostaglandins in normal subjects in an orthostatic position. Comparison with the response of the renin-aldosterone system].

Changes in blood pressure, plasma concentrations of PGE2, PGF2 alpha, G-keto-PGF1 alpha, thromboxane B2, aldosterone and plasma renin activity were evaluated in 13 normotensive subjects passing from supine to upright position. Orthostatism resulted in slight elevation of blood pressure and increase of all plasma prostaglandins (except PGE2), plasma aldosterone and plasma renin activity. A positive correlation was found in supine position between systolic arterial pressure and thromboxane B2 level (p less than 0.001). In upright position, however, blood pressure did not correlate with any of the hormones assayed. Orthostatism is a powerful stimulant of renin and aldosterone secretion but not so much of prostaglandin secretion. Basal arterial pressure is significantly influenced by thromboxane A2.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Thromboxane B2 in borderline and essential hypertensive patients.

Thromboxane B2 (TxB2) was measured in the venous and arterial plasma and in the urine of 15 borderline and 15 sustained essential hypertensive patients, and in the plasma and urine of 12 control normotensive age-matched subjects. Plasma and urine thromboxane B2 were significantly higher in both the borderline and sustained hypertensives than in the control normotensives. There was a significant positive correlation between urinary (i.e. renal)TxB2 excretion and the glomerular filtration rate, and between urinary TxB2 excretion and sodium excretion in the hypertensive but not in the normotensive subjects. Thromboxane A2 participates in pressure natriuresis.

Adolescent↗
PubMed1982

Effects of captopril on prostaglandin and natriuresis in patients with essential hypertension.

The antihypertensive, renal and hormonal effects of captopril were studied in 10 patients with essential hypertension. Captopril significantly decreased arterial blood pressure with a concomitant increase in glomerular filtration rate, natriuresis and kaliuresis and a significant selective increase in urinary (renal) prostaglandin E2; other plasma and urinary prostaglandin (F2 alpha, 6-keto-prostaglandin F1 alpha; thromboxane B2) were not significantly changed. The urinary prostaglandin E2 increase was observed even in patients with pretreatment subnormal prostaglandin E2 excretion. Increases in urinary prostaglandin E2 were significantly positively correlated with increases in urinary sodium concentration. It is concluded that the antihypertensive effect of captopril is mediated, at least partially, by prostaglandin E2 release from renal and extrarenal tissues. Captopril enhances natriuresis at a lower perfusion pressure.

Blood Pressure↗