Search PubMed⌕ Search

Biomedical subjects

R Düsing

Publications and source records attributed to R Düsing.

180 records · Page 10Linked to original sources
PubMed1978

Renal biosynthesis of prostaglandin E2 and F2alpha: dependence on extracellular potassium.

Since recent investigations have shown elevated urinary PGE2 and polyuria in hypokalemic animals which were reversed by PG synthesis inhibition with indomethacin, studies were undertaken to examine the effects of extracellular [K+] on renomedullary PG production in vitro. Slices of rabbit and human renal papilla were incubated in Krebs-Ringer HCO3- buffer, 95% O2-5% CO2, glucose 10 mM, HSA 4 gm/100 ml, for 30 min at 38 degrees C, with and without 1-14C-AA (10 micrometer). Measurments were made of total endogenous iPGE2 and iPGF2alpha production and radioactive AA leads to PGE2. In rabbit renal medulla values for iPGE2 (nmol/gm/30 min) were 252 +/- 20 at [K+] 0; 182 +/- 17 at [K+] 2.5 mEq/L; 163 +/- 18 at [K+] 5.5; and 129 +/- 17 [K+] 9.0 (p less than 0.005). iPGF2alpha was unaltered by changes in media potassium concentrations (6.8 +/- 0.9 nmol/gm/30 min at [K+] 0 and 6.2 +/- 0.8 at [K+] 9.0 MEq/L). In the human renal medulla iPGE2 was 9.5 +/- 1.6 nmol/gm/30 min at [K+] 0; 5.0 +/- 0.7 at [K+] 2.5 mEq/L; 5.3 +/- 0.3 at [K+] 5.5; and 4.6 +/- 1.0 at [K+] 9.0 (p less than 0.05). AA leads to PGE2 (nmol/gm/30 min) was 3.21 +/- 0.92 at [K+] 0; 2.47 +/- 0.57 at [K+] 2.5 mEq/L; 1.30 +/- 0.30 at [K+] 5.5; and 0.76 +/- 0.4 at [K+] 9.0 in rabbit medulla (P less than 0.005). It is postulated that direct stimulation of papillary PGE2 biosynthesis by low extracellular [K+] impairing the cAMP-generating response to vasopressin could represent the initial event in the pathogenesis of vasopressin-resistant polyuria.

Animals↗
PubMed1977

[Triamterene in the treatment of hypertension with hydrochlorothiazide and propranolol (author's transl)].

In 36 patients with essential hypertension the action and side effects of hydrochlorothiazide (25 mg/d), hydrochlorothiazide-triamterene (25 and 50 mg/d) and propranolol (160 mg/d) were investigated. Hydrochlorothiazide and hydrochlorothiazide-triamterene led to an average decrease of the systolic blood pressure by 21 and 30 mm Hg and of the diastolic pressure by 11 and 18 mm Hg. Propranolol alone decreased the systolic pressure by 35 mm Hg on average in 8 out of 16 patients. The diastolic pressure was lowered by 20 mm Hg. In the remaining 8 patients the systolic pressure, when propranolol was used alone, decreased by 21.3 mm Hg, the diastolic pressure by 11.3 mm Hg. Addition of hydrochlorothiazide-triamterene lowered pressures by a further 22.5 (systolic) and 10.6 (diastolic) mm Hg. No disturbances of the potassium or acid-base balance were observed using hydrochlorothiazide-triamterene.

Acid-Base Equilibrium↗
PubMed1977

The role of prostaglandins in the natriuresis of acutely salt-loaded rats.

Mechanisms determining the natriuresis in ECV expansion are not yet completely known. The present study was therefore performed to investigate (1) the extent to which prostaglandins (PG) are involved in the natriuresis of ECV expansion and (2) by which mechanisms PG may affect renal Na absorption. In nonexpanded rats the prostaglandin synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 16 Sprague-Dawley rats EVC expansion with isotonic saline corresponding to an increase in body weight of 10% was induced and maintained for 60 min. Ten animals received an oral dose of 10 mg/kg BW of INDO prior to ECV expansion. Six animals served as controls (C). Blood pressure (INDO: 132 +/- 4 (SE); C: 130 +/- 3 mm Hg), GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg BW), fractional K excretion (INDO: 32.1 +/- 2.6; C: 43.4 +/- 4.8%), CH2O and Na-k-ATPase activities in renal cortex, medulla and papilla did not significantly differ in either group. Significant differences were observed in urinary flow rate (INDO: 0.82 +/- 0.8; C: 1.82 +/- 0.23 ml/min/kg KG) and fractional Na absorption (INDO: 91.9 +/- 1.1; C: 81.7 +/- 1.2%). The results indicate that PG are involved in the natriuresis following acute expansion of the ECV and suggest that PG may inhibit the intrinsic tubular capacity for Na absorption in the rat.

Adenosine Triphosphate↗
PubMed1977

Effects of prostaglandin inhibition on intrarenal hemodynamics in acutely saline-loaded rats.

We studied the effect of inhibition of the prostaglandin (PG)-synthesizing enzyme system in female Sprague-Dawley rats following acute expansion of the extracellular fluid volume (ECV). In 57 conscious rats expansion of the ECV with isotonic saline corresponding to an increase in body weight of 10% was induced. Prior to ECV expansion 31 rats received indomethacin (10 mg/kg of body wt) by stomach tube. In six non-ECV-expanded rats indomethacin had no effect on glomerular filtration rate (GFR) and renal plasma flow (RPF). In ECV-expanded rats pretreated with indomethacin, GFR was unaltered but 125I-hippuran clearance decreased, and filtration fraction significantly increased. Intrarenal 86Rb distribution was similar in control and ECV-expanded rats. Indomethacin caused a slight increase in relative cortical 86 RB activity in non-ECV-expanded rats, but had no effect on intrarenal 86Rb distribution in ECV-expanded rats. No difference in intracortical glomerular perfusion was noted between control and ECV-expanded rats. In indomethacin-treated ECV-expanded rats an increase in relative inner cortical perfusion was observed. Absolute perfusion remained unaltered. Thus the decrease in total RPF was entirely due to decreased perfusion of outer cortical nephrons. Renal prostaglandins therefore may play a permissive role for physical factors to promote renal sodium excretion in acute ECV expansion via changes in intrarenal hemodynamics.

Animals↗
PubMed1976

Prostaglandins and renal function in acute extracellular volume expansion.

Mechanisms determining the natriuresis in ECV-expansion are not yet completely understood. The present study was therefore undertaken to investigate if prostaglandins (PG) are involved in the natriuresis of acute ECV-expansion and by which mechanisms PG may affect renal Na-absorption. In non-expanded rats the PG synthetase inhibitor indomethacin (INDO) had no effect on renal function. In 37 Sprague-Dawley rats ECV-expansion with isotonic saline corresponding to an increase in b.wt. of 10% was induced. Twenty-one animals received an oral dose of 10 mg/kg b.wt. of INDO prior to ECV-expansion. Sixteen animals served as ECV-expanded controls (C). GFR (INDO: 12.5 +/- 1.0; C: 10.5 +/- 0.9 ml/min/kg b.wt.) did not significantly differ in both groups. However, total renal plasma flow (RPF) (INDO: 22.9 +/- 1.8; C: 30.1 +/- 2.7 ml/min/kg b.wt.), urinary flow rate (INDO: 1.11 +/- 0.20; C: 1.93 +/- 0.21 ml/min/kg b.wt.) and urinary excretion of sodium (INDO: 141 +/- 26; C: 267 +/- 46 muEq/min/kg b.wt.) and potassium (INDO: 13.0 +/- 0.9; C: 19.8 +/- 1.7 muEq/min/kg b.wt.) markedly decreased in animals pretreated with INDO. The results indicate that PG are involved in the natriuresis of acute ECV-expansion and suggest, that PG may inhibit the intrinsic capacity for Na-absorption in more proximal parts of the nephron possibly via intrarenal physical factors.

Animals↗
PubMed1975

[Effect of chronic beta-adrenergic blockade on blood pressure and release of renin, aldosterone and cortisol in essential hypertension (author's transl)].

Blood pressure (BP), plasma renin activity (PRA) and plasma concentration of aldosterone (PA) and cortisol (PC) were determined in essential hypertensive patients before and after beta-adrenergic blockade with propranolol and prindolol. Serial measurements of PRA, PA and PC at 30 min intervals (8 p.m. to 6 a.m.) were performed in 8 patients. Administration of propranolol (50 mg three times daily) over a period of 4 weeks was followed by a significant reduction in BP, PRA and PA. PC remained unaltered. The pattern of rhythmic secretion of renin was abolished whereas that of aldosterone persisted at a lower level. Prindolol (10 mg three times daily) had a similar effect on BP as propranolol but failed to lower PRA and PA. Rhythmic secretion of renin was also markedly altered with prindolol in the absence of any change in rhythmicity of PA and PC. The hypotensive action of prindolol was not mediated via inhibition of renin release. The dissociation between PRA and PA rhythmicity indicates that during beta-adrenergic blockade diurnal rhythm of aldosterone secretion is not regulated by the renin-angiotensin-system. Rhythmicity of PC was normal, indicating that also ACTH-secretion was unaltered. Thus, under beta-blockade unchanged diurnal rhythm of aldosterone may be due to normal ACTH-secretion.

Adrenergic beta-Antagonists↗
PubMed1975

[Diagnosis and treatment of disorders of the potassium balance with special reference to infusion therapy].

Following a short review of the physiological regulation of body potassium diagnostic procedures to detect disturbances in potassium balance are cited. The limited value of serum potassium concentration is emphasized. Possible caused of potassium deficiency and prophylactic measures to prevent negative potassium balance are summarized including oral and parenteral potassium administration. A synopsis of the causes of hyperkalemia is followed by a description of therapeutical measures. Chronic hyperkalemia may be treated by oral or rectal administration of ion-exchange resins, while acute lifethreatening hyperkalemia is corrected by infusion of isotonic saline, glucose and insulin, and calcium gluconate as well as by correction of metabolic acidosis with sodium bicarbonate. In patients with intact renal function these measures will generally result in rapid correction of increased serum potassium levels.

Acid-Base Equilibrium↗
PubMed1975

[Infusion therapy in kidney diseases].

Body electrolyte and water balance as well as elimination of toxic metabolites depend on intact renal function. Acute azotemia of either prerenal, renal, or postreanal origin requires adequate fluid and electrolyte theraphy. Based on physiological regulation of protein metabolism and nitrogen balance parenteral nutrition of uremic patients with stable renal function is described. Sufficient caloric supplementation is required. Parenteral treatment to improve nitrogen balance in these patients is achieved by infusion of essential amino acids including histidine. The possible therapeutic value of keto-analogs is suggested by recent studies.

Amino Acids↗
PubMedDate not supplied

Na+/H+ exchange in hypertension and in diabetes mellitus--facts and hypotheses.

An enhancement of Na+/H+ exchange (NHE) in blood cells of selected patients with essential hypertension and with diabetic nephropathy has been described by various investigators. Recent studies have shown that enhanced NHE activity persists in immortalized lymphoblasts from these patients after prolonged cell culture and, thus, appears to be under genetic control. Available evidence strongly argues against a mutation in the encoding gene or an overexpression of the NHE. Immortalized cells from hypertensive patients with enhanced NHE activity display two-fold enhanced agonist-induced rises of the cytosolic free Ca2+ concentration and the underlying reason was identified as an increased activation of pertussis toxin (PTX)-sensitive G proteins. The molecular mechanism(s) of this phenomenon have not yet been elucidated. It appears likely that similar changes contribute to the enhanced NHE activity phenotype in diabetic nephropathy, although experimental evidence for this is still lacking. An enhanced activation of PTX-sensitive G proteins could explain many of the hitherto unexplained phenomena in essential hypertension, e.g. inheritance, increased vasoconstriction, hypertrophy of remodeling of arterial blood vessels and the heart, enhanced platelet aggregation etc. In diabetes the same defect could provide the basis for the susceptibility to nephropathy, e.g. by enhancing the deleterious effects of autocrine and paracrine growth factors. Thus, the experimental approach of immortalizing blood cells from patients with essential hypertension and diabetic nephropathy has opened new horizons in the identification of genetically fixed abnormalities in intracellular signal transduction which could contribute to both pathologies and which can now be studied without the confounding influences of the diabetic or hypertensive in vivo milieu.

Animals↗
PubMedDate not supplied

Simultaneous and continuous measurement of free concentration of valproate in blood and extracellular space of rat cerebral cortex.

Free concentration of valproate (VPA) was measured simultaneously and continuously in blood and in the extracellular space of cerebral cortex of rats by VPA-selective microelectrodes. Constant amounts of VPA were injected into the femoral vein with differing duration of injection. Immediately after drug application, the concentration of free VPA in blood and brain increased to a peak value, the degree of which increased with the speed of injection. Ten to 15 min after VPA injection, a plateau value was reached. This plateau value was equal in the extracellular space of cortex and in blood. The data indicate that VPA can "freely" cross the blood-brain barrier (BBB).

Animals↗
PubMedDate not supplied

Evidence for structural alterations in resistance arteries of patients with severe congestive heart failure.

Congestive heart failure (CHF) is characterized by an increase in total peripheral resistance. It was the specific aim of this study to investigate whether structural factors participate in the increased peripheral resistance that can be observed in severe heart failure. We determined forearm vascular resistance (FVR) at rest and after 10 min ischemia (Rmin; mm Hg/ml/min/100 ml) using venous occlusion plethysmography. Rmin was studied since it is largely dependent on the structural characteristics of resistance arteries. 24 patients with CHF [71.5 +/- 2.3 years; New York Heart Association (NYHA) functional class I-IV] with no history of arterial hypertension and casual arterial blood pressure < 140/90 mm Hg and 24 normotensive healthy control subjects (52.5 +/- 4.1 years) were included in our study. The patients were subdivided into those with 'mild' (NYHA class I and II; n = 10) and 'severe' (NYHA class III and IV; n = 14) heart failure. There were no significant differences between the two groups for echocardiographically determined ejection fraction and mean arterial blood pressure. Resting FVR averaged 40.5 +/- 4.4 mm Hg/ml/min/100 ml in control subjects and was 43.6 +/- 7.9 (nonsignificant vs. control) and 51.0 +/- 5 mm Hg/ml/min/100 ml (p < 0.05 vs. control) in patients with mild and severe CHF, respectively. No significant correlation between age and Rmin could be demonstrated in either the patient or the control group. Furthermore, Rmin did not differ between patients with mild CHF and control subjects. However, Rmin was significantly elevated in patients with severe CHF (5.7 +/- 0.39 mm Hg/ml/min/100 ml) as compared to patients with mild CHF (4.0 +/- 0.39 mm Hg/ml/min/100 ml; p < 0.05) and controls (4.5 +/- 0.26 mm Hg/ml/min/100 ml; p < 0.05). In conclusion, our study supports the concept that structural alterations contribute to the increased peripheral resistance in patients with heart failure. These changes are correlated with the severity of clinical symptoms.

Adult↗
PubMedDate not supplied

[Indomethacin kinetics and urinary excretion of prostaglandin E2 following oral administration of various dosage forms of indomethacin].

In a controlled crossover study healthy volunteers received a single oral dose of 75 mg indomethacin, 75 mg sustained-release indomethacin, or the new therapeutic system indomethacin Gits 7/85. Dependence on the time of administration was investigated by comparing the plasma level curves obtained following morning and evening administration of indomethacin and indomethacin Gits. Blood samples were taken at defined intervals following administration for determination of indomethacin plasma levels. To determine urinary excretion of prostaglandin (PG)E2, urine was collected during four consecutive 6 h-clearance periods after administration of the indomethacin preparations. The plasma level curve following administration of indomethacin Gits 7/85 did not exhibit clearly distinct initial peaks and, in contrast to the other drug preparations, remained nearly constant over 10-12 h. Indomethacin induced a significant suppression of urinary PGE2 excretion over a period of 12 h, whereas both sustained release indomethacin and indomethacin Gits 7/85 decreased urinary PGE2 excretion for 18 h. Neither the plasma concentration curve of indomethacin nor the inhibitory effect on urinary PGE2 excretion was dependent on the time of administration. Initial central nervous side effects, such as dizziness, were reported by all volunteers after taking indomethacin and by half of the volunteers following sustained release indomethacin, whereas no adverse effects were observed after administration of indomethacin Gits 7/85. The present study demonstrates that indomethacin Gits 7/85 produces no initial peaks of plasma levels but rather a sustained concentration plateau. The excellent tolerability of indomethacin Gits 7/85 is probably due to the lack of peak plasma concentrations.

Administration, Oral↗