Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indomethacin has been reported to potentiate the release of noradrenaline from sympathetic nerve endings in vitro and to increase urinary noradrenaline excretion in rats. We have studied the influence of indomethacin on plasma catecholamine levels in 10 normal men, using measurement of plasma renin activity (PRA) as an index of the pharmacodynamic effect of indomethacin. Both in the supine and standing positions indomethacin failed to alter the plasma concentrations of noradrenaline, adrenaline or dopamine, while PRA was markedly suppressed. It is concluded that in the intact human indomethacin does not influence catecholamine concentrations.
 ...
PMID:Plasma catecholamines in man are not influenced by the inhibition of prostaglandin synthesis. 46 21

Techniques are described in detail for the radioimmunological measurement of prostaglandin (PG) E2 and F2alpha in human urine. 50 ml urine samples are extracted with an organic solvent system and then purified by silicic acid column chromatography. The overall recovery after extraction and purification, calculated with labeled as well as unlabeled compounds, is in the order of 70%. The column eluates are assayed at 1:12-1:60 dilution in the "standard diluent" of the assay: 8 pg PGE2 or PGF2 alpha/ml of whole urine represents the lowest measurable concentration. A urine blank and a solvent blank were evaluated separately, subjecting 50 ml of urine obtained from an indomethacin treated subject ("PG-free" urine) or 50 ml of distilled water, respectively, to the extraction-purification procedures. Both were found not to interfere with the antigen-antibody reaction. Urinary PG-like immunoreactivity (LI) was characterized in terms of immunochemical and thin-layer chromatographic (TLC) behavior. Both urinary PGE2-LI and PGF2 alpha-LI behaved as authentic PGE2 and PGF2 alpha, upon dilution and on TLC. In 33 healthy female subjects (aged 19-58 yr), urinary excretion rates averaged 178 +/- 80 (mean +/- SD) ng/day for PGE2 and 498 +/- 181 ng/day for PGF2 alpha. In a group of 8 healthy men, both PGE2 and PGF2 alpha excretion rates were higher and more scattered than the female values. When two healthy women were given indomethacin (200 mg/day), urinary PGE2 and PGF2 alpha dropped to undetectable levels during the 4th day of drug therapy. Intravenous injection of furosemide (50 mg) in a female volunteer was followed by an immediate rise of urinary sodium, PGE2, PGF2 alpha and PGE2/PGF2 alpha ratio and plasma renin activity. In a 10 year old girl with Bartter's syndrome, urinary PG excretion rate was elevated with a 3 times higher than normal PGE2/PGF2 alpha ratio. Indomethacin therapy resulted in a prompt drop of PG excretion rate and of plasma renin activity. These results show that a combination of adequate purification steps and antisera with optimal characteristics provides a reliable method for measuring PGE2 and PGF2 alpha in urine, and therefore a valuable tool to further our knowledge of the physiology and physiopathology of the renal PG-system.
 ...
PMID:Radioimmunoassay measurement of prostaglandins E2 and F2alpha in human urine. 48 26

The effect of two prostaglandin synthesis inhibitors, indomethacin and meclofenamate, on angiotensin II (AII)- and III (AIII)-induced aldosterone release was studied in normal and sodium-depleted conscious rats and in adrenal capsular cell suspensions obtained from normal rats. In normal rats, in vivo AII and AIII were equipotent in causing dose-related increases in serum aldosterone concentrations. Indomethacin decreased the basal serum aldosterone levels by 50% and serum renin levels by 43%. In addition, the steroidogenic effects of AII and AIII were reduced by 45 and 63% with 3 mg/kg of indomethacin and 63 and 73% with 10 mg/kg, respectively. In contrast, meclofenamate failed to alter basal serum levels of aldosterone or AII-stimulated aldosterone release but inhibited serum renin levels by 27% and the aldosterone-stimulating effect of AIII by 99%. Indomethacin (3 mg/kg) and meclofenamate (2 mg/kg) inhibited urinary prostaglandin (PG)E(2) and PGF(2alpha) excretion by 63 and 52% and 37 and 31%, respectively. Both inhibitors significantly decreased the adrenal capsular PGE(2) and PGF(2alpha) content and the conversion of [(14)C]arachidonate to [(14)C]PGE(2) and [(14)C]PGF(2alpha). In sodium-depleted rats, indomethacin produced similar effects reducing the control serum aldosterone levels by 29%, AII-stimulated aldosterone by 47%, and completely suppressing the aldosterone response to AIII without altering serum renin activity. In adrenal cell suspensions, similar results were observed with indomethacin inhibiting basal and AII- and AIII-stimulated aldosterone release by 29, 81, and 93%, respectively. Meclofenamate failed to alter basal and AII-stimulated aldosterone release but inhibited that stimulated by AIII by 86%. The present findings suggest that prostaglandins modulate the effects of the renin-angiotensin system by stimulating the release of renin from the kidney and augmenting the steroidogenic effects of AII and AIII in the adrenal cortex.
 ...
PMID:Attenuation of angiotensin II- and III-induced aldosterone release by prostaglandin synthesis inhibitors. 50 Aug 24

Bilateral adrenalectomy combined with a sodium-deficient diet caused a time-dependent increase in plasma renin concentration in rats. Seventy-two hours after adrenalectomy the inhibitors of prostaglandin biosynthesis indomethacin and meclofenamate diminished the plasma renin concentration by about 50%. This effect was independent of the amount of renin released. Indomethacin and meclofenamate fully retained their ability to reduce the plasma renin concentration when the renal sympathetic nerves or the macular densa cells of the kidneys no longer contributed to renin release. It is concluded that in adrenalectomized rats renal prostaglandins effect the baro-receptor-mechanism in the afferent arterioles and thus enhance renin release.
 ...
PMID:Studies on the inhibitory effect of indomethacin and meclofenamate on the adrenalectomy-induced increase in plasma renin concentration. 52 95

A 2-year-old girl presenting with features of both Bartter's syndrome and renal tubular acidosis was investigated. Hypokalemia, increased plasma renin activity in the absence of hypertension, insensitivity to the pressor effects of angiotensin and a histological picture of juxtaglomerular hyperplasia were characteristic of Bartter's syndrome, but an unusual finding was the presence of metabolic acidosis instead of alkalosis. Functional studies revealed a proximal tubular defect in sodium and bicarbonate reabsorption and a distal defect in sodium reabsorption, urinary acidification and concentrating mechanism. Indomethacin administration was followed by an excellent clinical response and improvement of most functional abnormalities. The defect in distal sodium reabsorption was, however, not corrected by prostaglandin inhibition, and could represent the primary event leading to potassium wasting and secondary hypersecretion of prostaglandins.
 ...
PMID:Bartter's syndrome presenting with features resembling renal tubular acidosis. Improvement of renal tubular defects by indomethacin. 65 58

A 63-year-old man had asymptomatic Bartter's syndrome, discovered during evaluation for hypokalemia. Elevated plasma renin and aldosterone levels, angiotension resistance, and elevated urinary prostaglandin excretion were noted. Tubular function studies implicated the proximal tubule as the site of a mild sodium reabsorption defect, and renal wasting of potassium and magnesium were also noted. Indomethacin therapy lowered the urinary prostaglandin excretion and the renin and aldosterone levels but did not correct the hypokalemia. Spironolactone therapy resulted in normalization of serum potassium but not serum magnesium levels. Bartter's syndrome may result from various causes but renal wasting of sodium, potassium and/or magnesium probably exist in all cases. Unexplained, asymptomatic hypokalemia in any age group may be due to Bartter's syndrome.
 ...
PMID:Asymptomatic Bartter's syndrome. 71 82

1. A linoleic acid free diet and indomethacin treatment induce an increase in the epinephrine and norepinephrine concentrations in the plasma. 2. The renin activities in the kidney and plasma were increased by a linoleic acid free diet and decreased by indomethacin treatment. 3. The reactivity of isolated blood vessels to norepinephrine, angiotensin, PGE2 and PGA2 was intensified after linoleic acid free diet. Indomethacin treatment neutralized the differences between the different diet groups. We conclude that the increase in the sympathetic activity, in the renin activity and in the vasoreactivity after a linoleic acid free diet has promoted the elevation of blood pressure of salt loaded rats and that these prohypertensive changes have been caused by a diminished PG biosynthesis in kidneys and blood vessels.
 ...
PMID:Influence of linoleic acid in the diet on arterial pressure of salt loaded rats. II. Effects on plasma catecholamine concentration, renin activity, and reactivity of isolated vessels. 74 4

Urinary kallikrein in a patient with Bartter's syndrome was remarkably higher than normal. Indomethacin treatments increased serum potassium concentration and urinary Na/K ratio, and improved the response of blood pressure to angiotensin II infusion, while it decreased plasma renin activity, plasma aldosterone and urinary kallikrein. The purified urinary kallikrein had one component of the iso-electric point 4.3 by isoelectric focusing using Ampholine system, and its molecular weight was 4.2 x 10(4), which was greater than those of three components of normal human urinary kallikreins (normal HUK). Also Km values with TAME and BAME of urinary kallikrein in our patient with Bartter's syndrome did not correspond to those of normal HUK. Thus it can be said that urinary kallikrein in our patient with Bartter's syndrome was qualitatively different from normal HUK. The present observation might be a reflection of renal tubular dysfunction in this patient with Bartter's syndrome.
 ...
PMID:Quantitative and qualitative estimation of urinary kallikrein in a patient with Bartter's syndrome. 75 4

The effect of indomethacin on plasma renin activity (PRA), urinary aldosterone, 17 OH ketogenic steroids and plasma cortisol was studied in twenty-three patients with essential hypertension and compared in eleven patients to oxprenolol effect by 2 x 2 factorial trial. Indomethacin decreased PRA and urinary aldosterone: its effect was maintained when the drug was given for three days and it was related to basal PRA and aldosterone values. Therefore in patients with low PRA (renin-sodium index) PRA and aldosterone were unchanged, while they decreased in the normal high PRA group. Aldosterone changes were related to those of PRA, while 17 OH ketogenic steroids and plasma cortisol were unchanged. Both indomethacin and oxprenolol decreased PRA, but no interaction or additive effect was found between the two drugs. The present data indicate that indomethacin can decrease both PRA and aldosterone to an extent which is related to basal values and that aldosterone changes are mainly explained by those of PRA. The PRA unresponsiveness to indomethacin found in low renin patients may suggest renal prostaglandin deficiency. Finally the lack of interaction or of additive effect between indomethacin and oxprenolol may be explained by postulating either that the two drugs act on a common pathway or that an additive effect on PRA cannot be detected renin being maximally suppressed by full renal beta-receptors blockade.
 ...
PMID:The effect of indomethacin on plasma renin activity and urinary aldosterone of patients with essential hypertension. 75 81

1 The effects of frusemide (a diuretic acting on the loop of Henle) and methyclothiazide (a thiazide diuretic) on renin release were studied on rat kidney slices. 2 Frusemide at concentrations of 1.5 and 7.5 mmol/l produced significant increases in renin release but had no effect at 0.15 mmol/l. 3 Methyclothiazide in a similar concentration range did not increase renin release; instead, at the highest concentration used, methyclothiazide (3.5 mmol/l) inhibited renin release. 4 Indomethacin (25 mumol/l) did not inhibit the increase of renin induced by frusemide. 5 Our limited study in vitro is consistent with the findings of other workers who have shown in vivo, in the absence of systemic electrolyte depletion, that only "loop diuretics" increase renin secretion. Under our experimental conditions, it is suggested that frusemide exerts a direct action either upon the epithelioid cells or upon the macula densa since the renal prostaglandin system does not intervene.
 ...
PMID:A comparative study of the action of frusemide and methyclothiazide on renin release by rat kidney slices and the interaction with indomethacin. 76 Aug 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>