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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 855-858 
    ISSN: 1432-1440
    Keywords: Cushing's syndrome ; Pathogenesis of hypertension ; Renin angiotensin system ; Captopril
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To analyse the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome ten patients with hypercorticism (five with pituitary hypothalamic dysfunction, three with adrenal adenomas and two with adrenal carcinomas) received a single oral dose of 25 mg captopril. Mean arterial pressure was then determined at short intervals over periods of up to 240 min. Plasma renin activity (PRA) was measured immediately before the administration of captopril. Eleven patients with severe essential hypertension, who showed a comparable distribution of basal PRA values, served as a control. Patients with elevated basal PRA values (〉3 ng/ml·3 h) showed, both in the subgroup of cases with essential hypertension and in that with Cushing's syndrome, a statistically significant fall (P〈0.05−P〈0.001) in mean arterial pressure, the decrease being slightly more pronounced in essential hypertensives. On the other hand patients with normal PRA values (≦3 ng/ml·3 h) exhibited only a minor fall in mean arterial pressure reaching statistical significance (P〈0.05) only after 60 min (essential hypertension) and 180 min (Cushing's syndrome), respectively. Our results document that in patients with Cushing's syndrome the effect of captopril seems to be determined by the activity of the renin angiotensin system. Thus, in a substantial number of patients with hypercorticism, the renin angiotensin system may be an important factor in the pathogenesis of hypertension, whereas in patients with low PRA values other factors like oversecretion of mineralocorticoids may be responsible for the observed blood pressure increases.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 27-34 
    ISSN: 1432-1440
    Keywords: Regulation of aldosterone ; Anephric patients ; ACTH ; Angiotensin II ; Hemodialysis ; Aldosteronregulation ; Nierenlose Patienten ; ACTH ; Angiotensin II ; Hämodialyse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 14 anephrischen Patienten wurde der Einfluß von ACTH, Angiotensin II, Orthostase und Hämodialyse auf die Plasmaaldosteronkonzentration untersucht. Gleichzeitg wurden Plasmareninaktivität (PRA), Plasmacortisol, Serumnatrium und Serumkalium bestimmt. Unter 4stündiger Infusion von synthetischem ACTH (2,5 µg/min Synachten) kam es zu einem signifikanten Anstieg des Plasmaaldosterons und des Plasmacortisols (p〈0,025 bzw. 〈0,005), während Serumnatrium und Serumkalium unverändert blieben. Eine einstündige Infusion einer suppressorischen Dosis von synthetischem Angiotensin II (1,0 ng/kg Körpergewicht/min Hypertensin) führte zu einem geringgradigen, jedoch nicht signifikanten Anstieg des Plasmaaldosterons und hatte keinen Einfluß auf Plasmacortisol und Serumelektrolyte. Eine nach 60 min zusätzlich durchgeführte ACTH-Infusion (2,5 µg/min Synacthen) bewirkte über einen Zeitraum von 4 h einen ähnlichen Plasmaaldosteronansteig wie die alleinige ACTH-Infusion. Durch Orthostase ließ sich ein signifikanter Anstieg des Plasmaaldosterons (p〈0,05) erzielen, während Plasmacortisol und Serumelektrolyte keine signifikanten Veränderungen zeigten. Sowohl normale als auch isonatriämische und isokaliämische Hämodialyse führten zu einem vergleichbaren Anstieg des Plasmaaldosterons. Das Plasmacortisol blieb bei der normalen Hämodialyse unverändert und fiel bei der isonatriämischen und isokaliämischen Hämodialyse ab. Die Plasmareninaktivität war unter den beschriebenen Versuchsbedingungen mit ganz wenigen Ausnahmen nicht meßbar (〈0,2 mg/ml·3 h). Vereinzelt tiefnormale PRA-Werte wurden weder durch Hämodialyse noch Orthostase beeinflußt. Unsere Ergebnisse zeigen bei nierenlosen Patienten eine Stimulation des Plasmaaldosterons durch synthetisches ACTH, ein geringgradiges Ansprechen auf suppressorisches Angiotensin II, eine fehlende Potenzierung der ACTH-Wirkung durch suppressorische Dosen von Angiotensin II und einen Aldosteronanstieg unter Orthostase. Ferner ließ sich unter Hämodialyse ein Anstieg des Plasmaaldosterons beobachten. Dieser Anstieg trat sowohl unter normaler als auch unter isokaliämischer und isonatriämischer Hämodialyse auf und konnte deshalb ebenso wie die durch Orthostase induzierte Veränderung der Hormonkonzentration keinem der bekannten aldosteronstimulierenden Faktoren zugeordnet werden. Eine mögliche Beteiligung anderer Faktoren an der Aldosteronregulation ist deshalb anzunehmen.
    Notes: Summary The influence of ACTH, angiotensin II, orthostasis and hemodialysis on plasma aldosterone concentration was investigated in 14 anephric patients. Furthermore, plasma renin activity (PRA), plasma cortisol, plasma sodium concentration and plasma potassium concentration were measured. After infusion of synthetic ACTH (2.5 εg/min Synacthen) for 4 h a significant rise of plasma aldosterone concentration and plasma cortisol concentration was observed (p〈0.025,p〈0.005, respectively), whereas serum sodium and serum potassium concentrations remained unchanged. A slight though not statistically significant rise of plasma aldosterone concentrations was observed after 1 h-infusion of synthetic angiotensin II (1.0 ng/kg/min Hypertensin) while plasma cortisol concentration and serum electrolytes showed only minor changes. Sixty min after starting the infusion with angiotensin II ACTH (2.5 µg/min Synacthen) was infused additionally over a period of 4 h. Under the latter conditions as with ACTH alone an increase of plasma aldosterone concentration was observed. Orthostasis caused a significant rise in plasma aldosterone (p〈0.05), whereas plasma cortisol and the serum electrolytes remained unchanged. Conventional as well as isonatriaemic and isokaliaemic hemodialysis let to a comparable increase of plasma aldosterone. Plasma cortisol was unchanged during conventional hemodialysis, and showed a decrease after isonatriaemic and isokaliaemic hemodialysis. With a few exceptions plasma renin activity (PRA) was undetectable low (〈0.2 ng/ml·3 h). In those instances where low normal PRA values were found, these values were not influenced by hemodialysis or orthostasis. Our results show that in anephric patients plasma aldosterone increased in response to synthetic ACTH, orthostasis and hemodialysis. After the infusion of angiotensin II only a slight, statistically not significant increase in plasma aldosterone concentration was observed. The simultaneous infusion of ACTH and angiotensin II let to a comparable increase in plasma aldosterone as ACTH alone. Furthermore, hemodialysis let to an increase of plasma aldosterone under conventional as well as under isokaliaemic and isonatriaemic conditions. These changes in hormone concentration as well as those induced by orthostasis could not be explained by one of the known aldosterone stimulating factors. Thus, our findings suggest that other factors may be involved in the regulation of plasma aldosterone in anephric man.
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  • 3
    ISSN: 1432-1440
    Keywords: Renal artery aneurysm ; Renal cyst ; Hydronephrosis ; Coarctation of the aorta ; Radiation nephritis ; Hypertension ; Renin angiotensin system ; Nierenarterienaneurysma ; Nierencyste ; Hydronephrose ; Coarctatio aortae ; Strahlennephritis ; Hypertonie ; Renin-Angiotensin-System
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Studie wurden 19 Patienten mit seltenen Formen renaler Hypertonie untersucht: 6 Patienten mit Nierenarterienaneurysma, 6 Fälle mit unilateraler Hydronephrose, 4 Patienten mit unilateraler Nierencyste, 2 Fälle mit Coarctatio aortae und assozierter Nierenarterienstenose und ein Patient mit Strahlennephritis. Die Plasma-Renin-Aktivität (PRA) im Nierenvenenblut wurde bei 17 der 19 Fälle bestimmt. 7 dieser 17 (41%) Patienten zeigten einen signifikanten Seitenunterschied (PRA betroffene/PRA nicht betroffene Seite) ≧1,5. Der Prozentsatz positiver Tests war in verschiedenen Kollektiven vergleichbar hoch. Nur Patienten mit unilateraler Nierencyste zeigten in keinem Fall einen signifikanten PRA-Quotienten. Eine superselektive Nierenvenenrenin-Bestimmung bei 2 Patienten mit Nierenarterienaneurysma der oberen Segmentarterie zeigte in beiden Fällen eine erhöhte Plasma-Renin-Aktivität im Bereiche des Oberpols. 15 der 19 Patienten (79%) wurden operiert. Dabei kamen entweder plastisch rekonstruktive Verfahren oder eine Nephrektomie zur Anwendung. 4 Fälle mit Nierenarterienaneurysma wurden antihypertensiv behandelt. Patienten mit unilateraler Hydronephrose zeigten postoperativ die besten Ergebnisse (3 geheilt, 3 gebessert), während bei keinem der 4 Patienten mit unilateraler Nierencyste die Blutdruckwerte durch den operativen Eingriff normalisiert werden konnten (3 gebessert, 1 nicht gebessert). Die Patienten mit Coarctatio aortae und assozierter Nierenarterienstenose sowie die 2 operierten Fälle mit Nierenarterienaneurysma zeigten alle ein gutes Ansprechen auf den gefäßrekonstruktiven Eingriff (2 geheilt, 2 gebessert). Der Patient mit Strahlennephritis schließlich war 2 Jahre nach Nephrektomie gebessert. Im Gesamtkollektiv unserer operierten Patienten war die prognostische Aussagekraft der Nierenvenenreninbestimmung beschränkt. Allerdings erwies sich die selektive Nierenvenenreninbestimmung bei Patienten mit einem Aneurysma einer Nierensegmentarterie als nützlich zur Entdeckung lokaler Reninüberproduktion.
    Notes: Summary In the present study 19 patients with rare forms of renal hypertension were investigated: 6 patients with renal artery aneurysm, 6 cases with unilateral hydronephrosis, 4 patients with unilateral simple renal cyst, 2 cases with coarctation of the abdominal aorta and associated renal artery stenosis and 1 patient with radiation nephritis. Renal venous renin activity (PRA) was determined in 17 of the 19 cases. Seven of these 17 (41%) patients showed significant PRA-ratios (PRA affected/PRA unaffected side ≧1.5). The percentage of positive tests was comparably high in the various subgroups except in patients with renal cyst, none of them showing lateralisation of renin secretion. Selective sampling in 2 patients with renal artery branch aneurysm revealed in both cases marked local renin oversecretion. Fifteen of the 19 patients (79%) were operated either by reconstruction surgery or nephrectomy. Four cases with a renal artery aneurysm were treated with antihypertensive drugs. Patients with unilateral hydronephrosis showed the best response to surgery in terms of cure rate (3 cured, 3 improved), whereas blood pressure normalisation could not be achieved in patients with simple renal cyst (2 improved, 1 unimproved). Patients with coarctation of the abdominal aorta and associated renal artery stenosis and the 2 operated cases with renal artery aneurysm showed a good effect of corrective surgery (2 cured, 2 improved). The patient with radiation nephritis finally was improved 2 years after nephrectomy. For the total group the prognostic validity of renal venous renin determination was limited. However, selective blood sampling from peripheral renal veins may be useful in cases with renal artery branch aneurysm to detect local oversecretion of renin.
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  • 4
    ISSN: 1432-1440
    Keywords: Captopril ; Kidney function ; Essential hypertension ; Renovascular hypertension ; Renal parenchymatous hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study long-term effects of captopril on renal function in patients with various forms of severe hypertension, serum creatinine values were monitored in 76 patients under captopril therapy over a period of up to 3 years. Three different groups were formed: (1) patients with essential hypertension (n=37); (2) patients with renovascular hypertension (n=20); (3) patients with renal parenchymatous hypertension (n=19). In each of the three groups reduction in blood pressure was accompanied by increases in serum creatinine. However, both changes were more pronounced in patients with renovascular hypertension. In this group only the rise in creatinine was statistically significant and showed a slight progression with duration of captopril treatment. Group specific analysis revealed that the increase was smaller in patients with unilateral (n=16) renovascular disease than in those with bilateral (n=4) involvement, but in the former it was still significantly higher than in patients with essential or renal parenchymatous hypertension. Separation of patients according to the underlying disease of renovascular hypertension showed that renal function deteriorated less in patients with arteriosclerotic origin (n=10) than in those with fibromuscular dysplasia (n=8). Statistical evaluation of subjects with renovascular and essential hypertension still revealed significant differences in creatinine when the patients with initial plasma renin activity (PRA) below and above 6 ng/ml·3 h were compared separately. A significant correlation (r=0.73;P〈0.05) between blood pressure reduction and creatinine changes was obtained only for patients with renovascular hypertension. Finally, in all three groups of patients creatinine changes were statistically independent from daily dosages of captopril. From these data we conclude that sustained impairment of kidney function by captopril is mainly restricted to patients with renovascular hypertension and possibly results from the combined effects of low renal perfusion pressure and interference with intrarenal regulation of glomerular filtration rate by a postulated angiotensin-II-mediated mechanism.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 925-930 
    ISSN: 1432-1440
    Keywords: Transdermal therapeutic systems (TTS) ; Clonidine ; Essential hypertension ; Skin allergy ; Clonidine allergy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin patches of a clonidine transdermal therapeutic system (clonidine-TTS) with a constant release rate of either 0.1 or 0.2 mg clonidine/24 h continuously over 7 days were used in 32 essential hypertensives. These self-adhesive drug delivery systems (3.5 cm2), which were affixed to the upper outer arm, were changed by the patients at weekly intervals. During a mean observation period of 7 months (range 1–19 months) transdermal clonidine reduced the blood pressure from 162±15/107±5 mmHg to normal values (diastolic ≦95 mmHg) in 63% of our patients. However, chronic use of clonidine-TTS was accompanied by a high frequency of contact dermatitis (type IV allergy) in nearly half of our patients (n=15, 47%). In 11 of these 15 patients transdermal clonidine administration had to be stopped because of intolerable local skin reactions (pruritus, erythema, vesiculation, and/or infiltration). Subsequent patch testing with all components of clonidine-TTS was performed in eight cases. Whereas in seven cases an allergic contact dermatitis to clonidine was found, only one patient showed an allergy to another component of clonidine-TTS (polyisobutylene). We conclude that this strikingly high incidence of local allergic skin reactions limits the use of clonidine-TTS in essential hypertension.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 62 (1984), S. 470-476 
    ISSN: 1432-1440
    Keywords: Adrenal carcinomas ; Aldosterone secretion ; Hypokalemic alkalosis ; Operation ; Chemotherapy with o,p′-DDD
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study two patients with aldosterone-producing adrenal carcinomas are reported. The clinical features were characterized by hypertension and severe hypokalemia with muscular weakness, flaccid paralysis of arms and legs, diarrhea and polyuria. In both cases excessively high plasma aldosterone levels and suppressed plasma renin activity were found. In contrast to most other cases with aldosterone-secreting tumours plasma cortisol, urinary free cortisol excretion, 17-hydroxy- and 17-ketosteroids were in the normal range. There was no clinical evidence of oversecretion of sex hormones. After adrenalectomy blood pressure and serum potassium normalized and the clinical symptoms disappeared. Plasma aldosterone and urinary aldosterone secretion returned to normal, while plasma renin activity remained low. Three and a half and 6 months later primary aldosteronism and the associated clinical symptoms reappeared due to hormonally active metastases. After introducing the antitumour drug o,p′-DDD in patient 1 aldosterone secretion normalized and the clinical status of the patient markedly improved. However, 10 months after diagnosis the patient died due to a haemorrhage from a liver metastasis. In patient 2 tumour-invaded regional lymph nodes were surgically removed with only minor changes in the hormone pattern.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Geophysical prospecting 29 (1981), S. 0 
    ISSN: 1365-2478
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences , Physics
    Notes: A forward solution for the reflection response of a parallel stratified lossless medium characterized by discrete reflection coefficients and unequal layer delays, for a normally incident pressure source signal, is presented. The notation, which details the reflection history of each wavelet in a response record, facilitates systematic enumeration of all terms in the reflection impulse response model, the determination of compact closed form expressions for amplitudes and delays of multiply reflected wavelets, and the aggregation of dynamic analog groups. An equal delay time constraint on layer thicknesses leads then to the reflection sequence or synthetic seismogram structure as an infinite sum of wavelets by their order of reflection.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 232 (1981), S. 450-451 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 59-67 
    ISSN: 1432-1440
    Keywords: Captopril-treatment resistant hypertension ; Essential hypertension ; Renalparenchymatous hypertension ; Renovascular hypertension ; Captopril ; therapieresistente Hypertonie ; Essentielle Hypertonie ; Renalparenchymatöse Hypertonie ; Renovaskuläre Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Studie wurden 51 Patienten mit schwerer, auf eine standardisierte Dreiertherapie resistente Hypertonie (20 mit essentieller, 15 mit renovaskulärer und 16 mit renalparenchymatöser Hypertonie) mit dem oralen Converting enzyme Inhibitor Captopril behandelt. Die mittlere Behandlungszeit betrug 8,6 Monate für Patienten mit essentieller, 8,9 Monate für solche mit renovaskulärer und 9,9 Monate für Fälle mit renalparenchymatöser Hypertonie. In allen 3 Patientengruppen konnte ein ausgeprägter und anhaltender Blutdruckabfall beobachtet werden. Allerdings war sowohl der absolute Blutdruckabfall als auch die individuelle Blutdruckantwort bei Patienten mit renovaskulärer Hypertonie ausgeprägter als bei solchen mit essentieller und renalparenchymatöser Hypertonie. Diese Ergebnisse weisen damit auf einen stärkeren antihypertensiven Effekt von Captopril bei Patienten mit renovaskulärer Hypertonie hin. Unsere Resultate zeigen weiter, daß eine Monotherapie mit Captopril eher die Ausnahme als die Regel war. So benötigten über 90% der Patienten zusätzliche Gabe eines Diuretikums und ein weiterer Anteil der Patienten darüberhinaus die Gabe eines Betablockers (50% der Patienten mit essentieller, 38% der Fälle mit renalparenchymatöser und 26% der Patienten mit renovaskulärer Hypertonie). Die Plasma-Renin-Aktivität stieg unter Captoprilbehandlung erwartungsgemäß an, während die Plasma-Aldosteron-Konzentration und die Converting enzyme Aktivität abfielen. In 17,6% (n=9) der 51 Patienten konnten Nebenwirkungen (Exanthem, Pruritus, supraventrikuläre Extrasystolen, Tachykardie, Wasser- und Flüssigkeitsretention, Raynaud-Phänomen, unvollständiger und vollständiger Geschmacksverlust und Leukopenie) beobachtet werden. Unsere Ergebnisse zeigen, daß Captopril bei schwerer therapieresistenter Hypertonie ein potentes Antihypertensivum ist. Dabei war bei unseren Patienten eine Monotherapie mit Captopril eher die Ausnahme als die Regel. So benötigten die meisten Patienten zusätzlich ein Diuretikum und/oder einen Betablocker. Allerdings erfordern die Nebenwirkungen des Medikaments eine engmaschige und genaue Überwachung aller Patienten.
    Notes: Summary In this study 51 patients with severe hypertension (20 essential, 15 renovascular and 16 renalparenchymatous) resistant to a standardized triple therapy were treated with the oral converting enzyme inhibitor captopril. Mean treatment period was 8.6 in essential, 8.9 in renovascular and 9.9 months in renalparenchymatous hypertension. In each of the 3 groups a marked and sustained blood pressure reduction was observed promptly after introducing captopril. However, absolute fall in mean blood pressure as well as individual blood pressure response were more pronounced in renovascular than in essential and in renalparenchymatous hypertension demonstrating a higher blood pressure lowering activity of the converting enzyme inhibitor in the former. In addition, our results document that monotherapy with captopril was rather the exception than the rule. More than 90% of all patients required at least the addition of a diuretic and even a substantial percentage of patients needed as a third drug a betablocker (50% in essential, 38% in renalparenchymatous and 26% in renovascular hypertension). As expected renin activity increased under captopril whereas plasma aldosterone and converting enzyme activity decreased. Side-effects (skin rash, pruritus, supraventricular extrasystoles, tachycardia, water and fluid retention, Raynaud-phenomenon, incomplete and complete taste loss and leucopenia) occurred in 17.6% (n=9) of the 51 patients. Our results show that captopril is a potent blood pressure lowering agent in severe and therapy resistant hypertension. The vast majority of patients, however, required concomitant therapy with a diuretic and/or a betablocker. Finally, the frequency of drug induced side-effects necessitates a close and careful monitoring of all patients.
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  • 10
    ISSN: 1432-1440
    Keywords: Hereditary hypothalamic diabetes insipidus ; (125I)arg8-Vasopressin binding ; Mononuclear phagocytes ; 1-desamino-8-D-Arginine vasopressin ; Desensitization phenomena ; Hereditärer hypothalamischer Diabetes insipidus-(125I)Arg8-Vasopressin Bindung ; Mononukleäre Phagozyten ; Desensibilisierungsphänomene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die spezifische Bindung von (125I) Arg8-Vasopressin wurde an mononukleären Phagozyten des zirkulierenden Blutes bei drei Patienten (ein Mann, zwei Frauen) mit hereditärem hypothalamischen Diabetes insipidus analysiert. Die Bindung wurde dabei vor, während und nach der Therapie mit 1-deamino-8-D-Arginin Vasopressin ermittelt und mit den Kontrollwerten von fünfzehn Normalspendern (sieben Frauen, acht Männer) verglichen. Vor Therapiebeginn war die Bindungsaktivität der Radioligande mit 0,3±0,08 f Mole/2,2×105 Zellen/ml gegenüber den Kontrollen (0,23±0,04 f Mole/2,2 × 105 Zellen/ml) gesteigert. Die Zunahme der Bindung wurde durch ein Ansteigen der Rezeptorkonzentration auf der Zelloberfläche verursacht. Im Gegensatz hierzu war die Bindungsaktivität der Rezeptoren während und nach dem Absetzen der Therapie deutlich reduziert (0,1±0,05 f Mole/2,2×105 Zellen/ml). Die Dissoziationskonstanten der Hormonbindung vor Therapie (25±0,2 pM) entsprach nahezu der von Normalspendern (24±0,8 pM); dies bedeutet, daß trotz der verschiedenen klinischen Situationen die Rezeptoraffinität für Vasopressin unbeeinflußt blieb. Im Gegensatz hierzu betrug die Dissoziationskonstante während und 48 h nach Absetzen der Therapie 11±0,45 pM, welches einer Zunahme der Bindungsaffinität entsprechen dürfte. Aus diesen experimentellen Daten kann geschlossen werden, daß die Gewebe unbehandelter Patienten mit hereditärem hypothalamischen Diabetes insipidus eine gesteigerte Empfindlichkeit gegenüber Vasopressin besitzen, daß jedoch die Bindungskapazität während und sogar 48 h nach Absetzen der Therapie reduziert ist. Diese molekularen Vorgänge könnten durch Desensibilisierungsphänomene unter der Therapie mit 1-deamino-8-D-Arginin Vasopressin erklärt werden.
    Notes: Summary Specific binding of (125I) arg8-vasopressin to mononuclear phagocytes of the circulating blood was studied in 3 patients (one male, two females) with hereditary hypothalamic diabetes insipidus before, during and after therapy with 1-desamino-8-D-arginine vasopressin and compared with values of 15 normal donors (7 males, 8 females). Before therapy specific radioligand binding activity was considerably increased (0.3±0.08 fmoles/2.2×105 cells/ml) versus controls (0.23±0.04 fmoles/2.2×105 cells/ml). Increased binding was due to increase in receptor concentration per cell. In contrast, during treatment and after withdrawal of therapy the receptor binding activity was 0.1±0.05 fmoles/2.2×105 cells/ml. The dissociation constant (K D) for hormone binding before therapy (25±0.2 pM) was roughly identical with that of normal donors (24±0.8 pM), indicating insignificant changes in receptor affinity. During treatment and 48 h after withdrawal of therapy, however, theK D value was 11±0.45 pM, which may be accounted for by an elevation in the binding affinity. We conclude that untreated patients with hereditary hypothalamic diabetes insipidus have increased tissue sensitivity to vasopressin, but have decreased binding capacity during and even two days after discontinuation of therapy, possibly as the result of 1-desamino-8-D arginine vasopressin-induced desensitization phenomena.
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