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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 3 (1976), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Isolated rat kidneys were perfused at a constant pressure of 90 mmHg in a single-pass system with either a cell-free medium or a suspension of washed bovine red blood cells, free of the components of the renin-angiotensin system. In red blood cell perfused kidneys renal haemodynamics and sodium reabsorption corresponded closer to values observed in the intact rat than in cell-free perfused kidneys.2. In red blood cell-perfused kidneys in the absence of plasma renin substrate autoregulation of renal blood flow was almost complete at pressures above 90 mmHg, provided that perfusion pressure was changed rapidly.3. Renin release varied inversely with perfusion pressure within a pressure range from 50 to 150 mmHg; the greatest changes of renin release occurred, when perfusion pressure was reduced from 90 to 70 mmHg; maximal stimulation of renin release was observed at 50 mmHg. After reduction of perfusion pressure, renin release immediately started to rise and reached a new level within 5 min. Local reduction of perfusion pressure in small arteries and arterioles by the injection of microspheres induced a short-lasting decrease in renal plasma flow and a transient stimulation of renin release.4. High concentrations of furosemide stimulated renin release by a direct intrarenal mechanism.5. Isoproterenol stimulated renin release in low concentrations without a concomitant vasodilation, whereas high concentrations induced an increase in both renal plasma flow and renin release. The effects of isoproterenol were completely blocked by propranolol.6. Sodium nitroprusside induced similar increases in renal plasma flow, as did high concentrations of isoproterenol, but only a small and slow increase in renin release was observed.7. Angiotensin II (AII) suppressed renin release in concentrations corresponding to plasma levels measured in the intact rat independently of its vasoconstrictor effects, whereas vasopressin in antidiuretic concentrations did not affect renin release.8. AII, AI, synthetic tetradecapeptide renin substrate (TDP), crude and purified rat plasma renin substrate induced a dose-dependent reduction in renal plasma flow. SQ 20 881, a competitive inhibitor of converting enzyme, and low doses of l-Sar-8-Ala-AH (saralasin), a competitive antagonist of AH, did not change renal plasma flow, whereas high concentrations of saralasin had a vasoconstrictor effect on their own.9. Saralasin inhibited the vasoconstrictor effects of All and TDP to a similar degree. SQ 20 881 inhibited the vasoconstrictor effects of AI and purified renin substrate, but did not influence the actions of TDP and the crude renin substrate preparation.10. From these data it is concluded, that AI is converted into AH within the kidney at a rate of 1–2%. The vasoconstriction induced by the crude renin sub-strate probably does not involve the All receptors. TDP may act by itself on the AII receptors or via the direct intrarenal formation of AII. The vasoconstriction induced by purified renin substrate is probably due to the intrarenal formation of AI and its subsequent conversion to AII.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: Renal Hemodynamics ; Renal Autoregulation ; Microspheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated rat kidneys were perfused with either a modified Krebs-Henseleit solution containing a gelatine preparation (Haemaccel, 35 g/l) or with a suspension of washed bovine red blood cells (RBC). When perfusion pressure (PP) was varied repeatedly in the range between 30 and 210 mm Hg autoregulation of renal plasma flow (RPF) was almost complete in RBC perfused kindneys. Changes of PP by steps of 20 mm Hg at intervals of 5 min resulted in an incomplete autoregulation of RPF and glomerular filtration rate (GFR). Renin release (RR) was inversely related to PP in the range between 50 and 150 mm Hg, while perfusion at a pressure below or above that range had no further effect on RR. The most marked increase in RR was obtained, when PP was reduced from 90 to 70 mm Hg. After reduction of PP, an increase in RR was measurable within 1 min, and a maximum was reached after 5 min. In kidneys perfused with a cell-free medium at a PP of 45 mm Hg for up to 30 min, RR remained elevated for the entire period of pressure reduction. Injection of microspheres into the renal artery resulted in a prompt decrease of RPF, GFR and urinary sodium excretion, but the values returned towards control levels within 15 min; RR increased only transiently after a short initial fall.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 55 (1977), S. 917-919 
    ISSN: 1432-1440
    Keywords: Renovascular hypertension ; Saralasin ; Hemodynamics ; Hypertension ; Renovasculäre Hypertonie ; Saralasin ; Hämodynamik ; Hypotension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 7 Patienten mit Hypertonie bei einseitiger Nierenarterienstenose sowie einem Patienten mit Hypertonie bei einseitiger pyelonephritischer Schrumpfniere wurde der Einfluß des Angiotensin II-Antagonisten Saralasin auf die Hämodynamik untersucht. Die Infusion von Saralasin führte bei Patienten mit normalem Plasmarenin zu einer Erhöhung des peripheren Gesamtwiderstands, bei erhöhtem Renin zu einer Widerstandsabnahme. Bei extrem erhöhten Reninwerten, die bei 3 Patienten unter forcierter Kochsalzverarmung beobachtet wurden, führte Saralasin zu einem bedrohlichen Blutdruckabfall mit zusätzlicher starker Verminderung des Herzminutenvolumens und des zentralvenösen Drucks; die Herzfrequenz stieg dabei entweder nicht oder nur geringfügig an. Die Befunde sprechen dafür, daß bei Patienten mit hohem Plasmareninspiegel der periphere Gesamtwiderstand, der Venentonus und damit der venöse Rückstrom zum Herzen und das Herzzeitvolumen wesentlich vom zirkulierenden Angiotensin II reguliert wird.
    Notes: Summary In 7 hypertensive patients with renal artery stenosis and in 1 patient with hypertension and unilateral pyelonephritic nephrophthisis the influence of the angiotensin II antagonist, saralasin on systemic hemodynamics was studied. In the patients with normal renin infusion of saralasin produced an increase in total peripheral resistance, in patients with elevated renin a decrease in peripheral resistance was observed. In 3 patients who had extremely high renin levels while under sodium depletion saralasin produced a dangerous drop in blood pressure concomitant with a marked decrease in cardiac output and in central venous pressure, heart rate remained unchanged or increased just slightly. The findings suggest that in patients with high plasma renin peripheral resistance, venous tone, venous return, and cardiac output are to a large extent controlled by circulating angiotensin II.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 293-301 
    ISSN: 1432-1440
    Keywords: Elimination ; Renal clearance ; Hydroxyethyl starch 200/0.5 ; Dextran 40 ; Oxypolygelatine ; Elimination ; Renale Clearance ; Hydroxyäthylstärke 200/0,5 ; Dextran 40 ; Oxypolygelatine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach Entzug von 400 ml Vollblut und anschließender Infusion von 500 ml eines kolloidalen Plasmaersatzmittels wurde bei 40 Probanden die intravasale und renale Kolloidelimination untersucht. Die einzelnen kolloidalen Lösungen waren nach folgenden Zeiträumen nicht mehr im Intravasalraum nachweisbar: 10% Hydroxyäthylstärke 200/0,5 (Anthron-Methode) nach 6 Wochen, 10% Dextran 40 (Anthron-Methode) nach 2 Wochen, 6% Hydroxyäthylstärke 200/0,5 (Anthron-Methode) nach 4 Wochen und 5,5% Oxypolygelatine (Hydroxyprolin-Methode) nach-2 Tagen. Kolloidale Plasmaersatzmittel stellen polydisperse Lösungen mit unterschiedlichem Molekulargewicht und Hydroxyäthylierungsgrad und deshalb auch mit einer Vielzahl unterschiedlicher Eliminationskonstanten dar. Bei wiederholter Applikation verschiebt sich die intravasale Kolloidkonzentration zu Gunsten der schwer eliminierbaren Moleküle mit längerer Halbwertzeit. Die Elimination der klinisch eingesetzten Dextran 40- und Oxypolygelatine-Lösung ließ sich am besten mit einem offenen 2-Kompartiment-Modell beschreiben. Die Elimination der mittelmolekularen Hydroxyäthylstärke 200/0,5 war als Ausdruck ihrer größeren Heterogenität auch unter Annahme von drei Eliminationskonstanten nur näherungsweise zu charakterisieren. In den ersten 4 Tagen wurde die Hydroxyäthylstärke 200/0,5 im Vergleich zu Dextran 40 rascher eliminiert. Anschließend aber fand sich für ca. 3% der zugeführten Hydroxyäthylstärke 200/0,5 eine wesentlich langsamere Elimination aus dem Intravasalraum. Besonders schnell wurde Oxypolygelatine ausgeschieden. Dementsprechend fand sich für Oxypolygelatine die größte renale Clearance, die eine enge Beziehung zum Molekulargewicht zeigte. Andererseits bedeutet eine rasche Elimination gleichzeitig eine entsprechend geringere Volumenwirkung.
    Notes: Summary After withdrawal of 400 ml whole blood and subsequent infusion of 500 ml of a colloidal plasma substituent, the intravascular and renal colloid elimination was investigated in 40 test subjects. The individual colloidal solutions could no longer be demonstrated in the intravascular space after the following times: 10% hydroxyethyl starch 200/0.5 (anthrone method) after six weeks, 10% dextran 40 (anthrone method) after two weeks, 6% hydroxyethyl starch 200/0.5 (anthrone method) after four weeks and 5.5% oxypolygelatine (hydroxyproline method) after two days. Colloidal plasma substitutes are polydisperse solutions with various molecular weights and degree of hydroxyethylation and therefore, also have a large number of different elimination constants. With repeated application, the intravascular colloid concentration shifts in favour of the molecules with a longer half life which are difficult to eliminate. The elimination of the clinically employed dextran 40 and oxypolygelatine solution could be best described with an open two-compartment model. As a result of its greater heterogeneity, the elimination of the moderately high molecular weight hydroxyethyl starch 200/0.5 could only be characterized approximately even assuming three elimination constants. In the first four days, the hydroxyethyl starch 200/0.5 was more rapidly eliminated compared to dextran 40. However, subsequently a very much lower elimination from the intravascular space was found for about 3% of the administered hydroxyethyl starch 200/0.5. Oxypolygelatine was eliminated especially rapidly. Accordingly, the greatest renal clearance was found for oxypolygelatine, which showed a close relation to the molecular weight. On the other hand, a rapid elimination simultaneously is followed by a correspondingly lower volume effect.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Labetalol ; Essential hypertension ; Plasma noradrenaline ; Noradrenaline infusion ; Plasma renin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 14 patients with essential hypertension, the influence of theα- andβ-adrenoceptor blocking drug labetalol on blood pressure, heart rate, plasma renin, plasma noradrenaline and pressor effect of exogenous noradrenaline was investigated during long-term treatment. During the initial four weeks of treatment, labetalol at a dose of 400 mg/day showed a slight effect only on supine blood pressure, whereas upright blood pressure was already lowered effectively after the second week of treatment (p〈0.01). An increase in the mean dose to 850 mg/day had an additional blood pressure-lowering effect (p〈0.001), whereby a preferential decrease of the orthostatic blood pressure was no longer apparent. Further increase in the mean dose to 1,000 mg/day at the end of the 12th week did not have an additional blood pressure-lowering effect. Body weight, plasma renin and plasma noradrenaline remained unchanged on labetalol treatment in the lowest and the highest dose. There was, however, an increased pressor effect of exogenous noradrenaline, i.e. anα-adrenoceptor antagonistic effect of labetalol was not detectable under these conditions. The cause of the increased pressor effect was a reduced climination of noradrenaline from plasma, which is probably the consequence of an inhibition of the uptake1 process by labetalol. During long-term treatment with the doses administered, the blood pressure-lowering effect of labetalol appears essentially to be the expression of theβ-adrenoceptor blocking properties of the drug.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 319 (1984), S. 434-435 
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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