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Biomedical subjects

B Scherer

Publications and source records attributed to B Scherer.

At least 55 records · Page 3Linked to original sources
PubMed1979

Formation and action of prostaglandins in the kidney.

The kidney has a high capacity to produce a spectrum of different acting prostaglandins (PG). In vivo and in vitro studies have shown that renal formation of PG's, possibly in the vasculature of the cortex represents an essential step in the mechanisms regulating the secretion of renin. PG's formed in the cortex seem to participate also in the control of renal vascular resistance and glomerular filtration rate. PGE2 formed in the medulla modulates the hydroosmotic action of antidiuretic hormone and influences the kidney's capacity for urine concentration. Renal PG formation is reduced by high NaCl intake and enhanced by low NaCl intake and in hypokalemic states. These findings make renal PG's good candidates for participation in the regulation of salt and water balance and in the control of blood pressure. Due to the close connection with the renin angiotensin system, alterations in renal PG formation might be involved in the etiology of high and low renin states. Thus, an impairment in the renal cortical production of vasodilating and renin-stimulating PG's could constitute the common denominator for both the reduced renin secretion and the increased vascular resistance which have been reported to be associated in essential hypertension.

Animals↗
PubMed1979

[Reduced urinary prostaglandin E2-excretion and diminished responsiveness of plasma renin activity in patients with essential hypertension (author's transl)].

Under basal conditions prostaglandin (PG) E2-excretion was significantly lower in 35 patients with essential hypertension studied than in 22 age- and sex-matched controls (p less than 0.02). PGF 2 alpha--excretion was similar in both groups. Within the first 15 minutes after furosemide i.v., PGE2-excretion rose substantially less in the patients than in the controls (p less than 0.001), while the increase in PGF 2 alpha-excretion was not different for both groups. The coincident rise of plasma renin activity was significantly lower in the hypertensive (167% +/- 11, SEM) than in the normotensive (386% +/- 46) group (p less than 0.001). Our results support the assumption that a decrease in renal cortical (vascular?) synthesis of vasodilatating PG's may be the cause for both, the diminished secretion of renin and the increase of vascular resistance in the kidney, which are often associated in essential hypertension.

Adult↗
PubMed1979

[Prostaglandins in cardiovascular and renal function. Biochemical, physiological and clinical findings (author's transl)].

Prostaglandins (PG) are highly unsaturated, cyclic fatty acids with 20 carbon atoms which are biosynthesized from dihomo-gamma-linolenic, arachidonic and eicosapentaenoic acids. These fatty acids are either ingested or are biosynthesized from linoleic and linolenic acids, respectively. The PG-precursor fatty acids are liberated from membrane phospholipids by phospholipase A and are converted to prostaglandins by the multienzyme complex PG-synthetase. The activity of the PG-system is influenced by extracellular hormonal, neural and mechanical stimuli and by intracellular factors such as ion-concentration and activity of the enzymes adenyl- and guanylcyclase. Prostaglandins are tissue hormones or autacoids which act on their receptors near their site of synthesis and degradation. The prostaglandin family constitutes a group of more than 10 natural occurring compounds showing a variety of biological actions. In arteries and veins the different PG:s have vasodilating as well as vasoconstricting effects. In addition, they are involved in the regulation of vascular smooth muscle proliferation. Within the kidney PG:s have vascular and tubular actions. They antagonize the effect of ADH, mediate renin secretion and are involved in the control of electrolyte balance. In the regulation of platelet aggregation and platelet adhesion PG:s have opposite functions: Prostacyclin which is synthesized in the vascular wall antagonizes the aggregating action of Thromboxane A2 which is formed in the platelets. A defect or an imbalance in the production of PG:s in the vascular wall, in platelets or in the kidney is assumed to play a pathogenetic role in a variety of cardiovascular and renal diseases such as in hypertension, atherosclerosis, persistent ductus arteriosus and Bartter's syndrome.

Arteriosclerosis↗
PubMed1979

Renal prostaglandins: relationship to the development of blood pressure and concentrating capacity in pre-term and full term healthy infants.

The relationships between urinary prostaglandins (PGs)E2 and F2 alpha and the postnatal development of blood pressure and renal concentrating capacity were investigated in 14 pre-term and 32 full term healthy infants. Mean PGE2 and PGF2 alpha excretion was 18.9 and 10.1 ng/h/1.73 m2, respectively, in pre-term infant. In full term infants mean urinary PGE2 was significantly lower (13.4 ng/h/1.73 m2) and PGF2 alpha significantly higher (22.2 ng/h/1.73 m2). The decrease of the PGE2/PGF2 alpha ratio (P less than 0.001) was accompanied by an increase in blood pressure. High PGE2 levels in pre-term infants were inversely correlated with urinary cAMP excretion. A decreasing PGE2/PGF2 alpha ratio in full term infants was associated with increasing urinary osmolality. After intranasal administration of antidiuretic hormone (DDAVP) in 8 full term infants the increase in urinary osmolality and cAMP excretion was accompanied by a drop in PGE2 excretion to less than half the basal values. These findings suggests that the postnatal changes in urinary PG excretion are associated with a concomittant increase in blood pressure and in the concentrating capacity of the neonatal kidney.

Blood Pressure↗
PubMed1979

Time-dependent changes in prostaglandin excretion in response to frusemide in man.

1. To evaluate in man by a non-invasive technique the possible role of prostaglandin (PG) compounds in initial renal haemodynamic effects after frusemide we studied the urinary excretion of PGE2 and of PGF2 alpha before and at 15 min and 120 min after intravenous injection of this drug. 2. An increase of PGE2 and of PGF2 alpha excretion was found in all 19 volunteer subjects within 15 min after frusemide, and PG excretion had returned towards control values at 120 min. The stimulation of PGF2 alpha excretion by frusemide was markedly lower in men than in women, but this difference was statistically not significant. 3. No clear-cut relation was found between urinary PG compounds, on the one hand, and urinary volume, urinary sodium and urinary potassium, on the other hand, during the study. 4. The results support the assumption that the rapid increase of urinary PG compounds after frusemide, which parallels the changes in renal haemodynamics, may be an indicator of an activation of the PG system, in part or predominantly, in the vascular compartment.

Adult↗
PubMed1979

Urinary prostaglandins and kallikrein in essential hypertension.

1. Urinary prostaglandins (PG), kallikrein and plasma renin activity (PRA) were measured in 35 patients with essential hypertension and 22 normotensive controls before and 15 min after frusemide (40 mg intravenously). 2. PGE2 and kallikrein excretion rates were lower in hypertensive subjects, and failed to rise to the same extent after frusemide. PGF2 alpha excretion was not significantly different in the two groups of patients either before or after frusemide. PRA rose less in the hypertensive subjects after frusemide. 3. These findings support the view that there is an abnormality of renal vasodilator systems (PGE2 and kallikrein) in essential hypertension.

Adult↗
PubMed1978

Prostaglandin (PG) analysis in urine of humans and rats by different radioimmunoassays: effect on PG-excretion by PG-synthetase inhibitors, laparotomy and furosemide.

The radioimmunological (RIA) determination of prostaglandin (PG) E2 and of PGF2alpha in urine of humans and rats is described in detail. After extraction and chromatography PGE2 was determined by using a PGE specific antibody or by using either PGB or PGF2alpha specific antibodies after the respective conversion procedures. The three different RIA procedures were compared to each other. PGF2alpha was determined by a specific antibody to PGF2alpha. Basal excretion of PGE2 and of PGF2alpha in healthy women on free diet was 9.3 ng/hour+/-0.98 and 18.3 ng/hour +/- 2.5 respectively. Furosemide increased the excretion of PGE2 and of PGF2alpha in humans significantly, while PG-excretion rates decreased on indomethacin. In rat urine PGE2 and PGF2alpha increased markedly from 46.2 pg/min +/- 9.3 and 27+/- 3.4 to 253.8 +/- 43.3 and 108 +/- 12.6 pg/min (per one kidney) in the anesthetized-laparotomized animal. This increase was abolished after giving two different PG synthetase inhibitors.

Adult↗
PubMed1978

[Pathogenetic, pathophysiological and biochemical aspects of essential hypertension (author's transl)].

Hereditary and environmental factors are involved in the pathogenesis of essential hypertension. Obesity, salt intake and stress are predominant among the environmental influences. Autonomous nervous dysfunction, increased contractility of vascular smooth muscle cells and impaired renal handling of sodium are major abnormalities in essential hypertension. At present it cannot be decided if alterations in the activities of systemic or renal hormonal systems reflect primary defects or adaptive changes in the regulation of blood pressure. In any case the kidney is regarded to have a key position in the long term increase of blood pressure in essential hypertension. Recent studies in essential hypertensive patients suggest that renin release decreases as renal vascular resistance increases. Studies from our laboratory have shown that renal prostaglandins are intrinsic to the renin release mechanism from the kidney. Additionally, there is evidence that renal prostaglandin synthesis is disturbed in essential hypertension, either primarily or secondarily, leading to unresponsive renin secretion. Further studies on the interrelationships of other hormonal systems and on hormone-receptor interactions in the vascular wall are necessary to delineate more precisely the mechanisms which are operative in the pathogenesis and manifestation of essential hypertension.

Adrenal Cortex Hormones↗
PubMed1977

Reversal of "one kidney" to "two kidney" tipe of Goldblatt hypertension in a patient with bilateral artery stenosis.

A 32-year old hypertensive woman with bilateral renal artery stenosis of more than 50% on both sides was studied. Renal vein renin levels were low (0.3 ng/ml/h on the right side and 0.42 on the left) before surgical correction of the left renal artery. Thereafter, blood pressure was only temporarily reduced. Four months later a repeat angiography demonstrated a widely patent left renal artery and the stenosis on the right side was unchanged. Renal vein renin was 5.12 on the left and 11.2 on the right. Subsequent operation on the right side lead to normalization of blood pressure. Thus, our patient seems to demonstrate in sequence the characteristics of the tow types of experimental renovacular hypertension known as "one kidney hypertension" and "two kidney hypertension". Our findings usggest that the pathomechanisms of these experimental models are operative in man too.

Adult↗
PubMed1977

Increase of free arachidonic acid by furosemide in man as the cause of prostaglandin and renin release.

Arachidonic acid (C20 :4) plasma renin activity (PRA), PGF2alpha, and sodium excretion were determined before and after furosemide in men. C20 : 4 and PRA increase (p less than 0.005) within 10 min after furosemide, PRA then decreased again whereas C20 : 4 levels remained elevated. Maximal exretion of PGF2alpha and sodium occurred 30-60 min after furosemide. Indomethacin prevented the rise of C20 : 4, PRA and PGF2alpha after furosemide, leaving sodium excretion unaltered. The release of C20 : 4 is assumed to be the primary mechanism of furosemide to increase PG biosynthesis and renin release.

Adult↗
PubMed1977

Radioimmunological and biological measurement of prostaglandins in rabbit urine: decrease of PGE2 excretion at high NaCl intake.

The estimation of prostaglandin (PG) E2 and of PGF2alpha by radioimmunoassay is described in detail. PGE2 was measured after conversion to either PGB2 or PGF2alpha and the results compared to bioassay. The methods were used to follow the excretion of PGE2 and PGF2alpha after salt loading in rabbits. A marked reduction of PGE2 levels was observed at high NaC1 intake, while PGF2alpha excretion remained unchanged.

Animals↗
PubMed1975

The binding of atractylate and carboxy-atractylate to mitochondria.

35S-labelled atractylate and carboxy-atractylate are produced biosynthetically and used for studying the binding of these specific ligands to the ADP, ATP carrier in beef heart mitochondria. The following results are obtained. 1. Inhibition of translocation activity goes parallel to the increase of binding by [35S]atractylate. No additional binding is observed after full inhibition of translocation is reached giving evidence that atractylate binds exclusively to the carrier. 2. The maximum number of binding sites of both atractylates is about 1.6 mumol/g protein in beef heart mitochondria and decreases on treatment of the membrane by Pi, freezing, ageing, etc. The dissociation constants of the binding are approximately for atractylate Kd = 5-10(-8) M and for carboxy-atractylate Kd = 10(-8) M. The mass action plots of the concentration dependence for the binding are nonlinear-convex in particular with carboxy-atractylate and more linear with atractylate. Nonlinearity appears to be caused by some retardation of equilibration in the case of very high affinity binding. 3. The binding of atractylate and carboxy-atractylate is relatively fast in intact mitochondria and slower in aged membranes. There is a slower and a faster binding portion. 4. The atractylates remove ADP in a nearly 1:1 stoichiometry from untreated mitochondria. In aged and Pi-treated membranes the ratio deltaADP/deltaatractylate approaches 0. Obviously binding of carrier sites to ADP is more sensitive to alterations than that of the atractylates. The assumption is maintained that the binding site for atractylate is identical with that for ADP and ATP. 5. Bongkrekate prevents binding of both atractylates. However, when added after, it only removes atractylate but not the carboxy compound because of its different tight binding. The removal of atractylate depends on the synergistic effect of bongkrekate with ADP. 6. The binding studies with [35S]atractylate and in particular the interaction with bongkrekate support the reorienting carrier model in which atractylate as an impermeable ligand fixes the binding site of the carrier outside while with bongkrekate the carrier site is turned to the inside.

Animals↗